Affinage

EXO1

Exonuclease 1 · UniProt Q9UQ84

Length
846 aa
Mass
94.1 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EXO1 is a conserved 5'→3' double-stranded DNA-specific exonuclease of the Rad2 nuclease family that acts at the convergence of mismatch repair, DNA double-strand break (DSB) repair, telomere maintenance, and replication fork processing (PMID:9207118, PMID:9685493, PMID:9823303). Its catalytic chemistry depends on conserved active-site aspartates (D78/D173/D225 in human EXO1), is stimulated by a 5'-phosphate, and proceeds along the minor groove of flap/duplex DNA downstream of the junction (PMID:11842105). In mismatch repair EXO1 excises mismatch-containing DNA and is recruited by direct tethering to Msh2-Msh6 through C-terminal SHIP-box peptides and to Mlh1 through an adjacent MIP box; these tethering motifs are redundant for MMR in vivo, and EXO1 additionally contributes a non-catalytic scaffolding role stabilizing MMR complexes alongside Exo1-independent (Pms1-endonuclease and Rad27) MMR branches (PMID:30061603, PMID:11438669, PMID:34552065). In DSB repair EXO1 performs long-range 5'→3' end resection downstream of MRX/MRN-Sae2 initiation, acting in parallel with the BLM/Sgs1-DNA2 pathway to generate the ssDNA required for RPA/Rad51 loading, HR, and the ATM-to-ATR checkpoint transition (PMID:18806779, PMID:18805091, PMID:21325134, PMID:21490081, PMID:22326273). Resection is gated by the local nucleoprotein environment: MRX/MRN and the SOSS1/SSB1 complex recruit EXO1 and enhance its processivity, PCNA promotes processivity through a C-terminal interaction, PAR binding via the PIN domain drives early recruitment, and histone marks (uH2B, H4K8ac) license recruitment, whereas Ku antagonizes EXO1 loading at break ends and RPA strips EXO1 from ssDNA to limit resection extent (PMID:20834227, PMID:21325134, PMID:23178594, PMID:23939618, PMID:26400172, PMID:32966758, PMID:26067273, PMID:26884156). EXO1 likewise generates ssDNA at uncapped or dysfunctional telomeres and at stalled/reversed replication forks and G-quadruplex barriers, coupling end processing to checkpoint activation (PMID:12154123, PMID:15454530, PMID:15629726, PMID:32232411). During meiosis EXO1 has two genetically separable functions—catalytic DSB resection and a non-nuclease role coordinating crossover resolution by constitutively binding MutLγ (Mlh1-Mlh3) and recruiting Cdc5/polo kinase to crossover sites (PMID:21172664, PMID:33199619). EXO1 activity is tightly restrained by phosphorylation (ATM, ATR, CDK1/2, AMPK), sumoylation, and SCF/Cullin-RBX1-mediated ubiquitin-proteasome degradation, which collectively tune the timing and extent of resection across the cell cycle (PMID:18756267, PMID:24705021, PMID:28515316, PMID:31053472, PMID:31562368, PMID:26083678). EXO1 is essential for the viability of BRCA1-deficient cells through its requirement in single-strand annealing repair (PMID:38266640).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 1997 High

    Establishing EXO1's identity required showing it is a dedicated dsDNA 5'→3' exonuclease physically and genetically linked to mismatch repair rather than a generic nuclease.

    Evidence Two-hybrid, reciprocal Co-IP with MSH2, and mutator/epistasis genetics in S. cerevisiae

    PMID:9207118

    Open questions at the time
    • Did not establish whether the MSH2 interaction is direct or bridged
    • Catalytic mechanism not yet defined
  2. 1998 High

    Functional conservation was unknown; human EXO1 was shown to be an enzymatically active Rad2-family exonuclease that complements yeast, validating the human ortholog.

    Evidence In vitro nuclease assay with recombinant human protein plus yeast rad27 complementation

    PMID:9685493 PMID:9823303

    Open questions at the time
    • Did not define which repair pathways human EXO1 acts in vivo
    • Regulation of activity unaddressed
  3. 2002 High

    How EXO1 engages substrate was unclear; active-site residues and DNA-binding geometry were mapped, defining the catalytic and substrate-recognition basis of nuclease function.

    Evidence Site-directed mutagenesis, in vitro nuclease assays, and hydroxyl radical footprinting of human Exo1

    PMID:11842105

    Open questions at the time
    • No high-resolution structure of the enzyme-DNA complex
    • Did not address regulation by partner proteins
  4. 2004 Medium

    EXO1's role beyond MMR was unknown; it was shown to generate ssDNA at uncapped/dysfunctional telomeres and to be required for the resulting checkpoint arrest.

    Evidence Quantitative ssDNA detection (QAOS) and cell-cycle assays in yku70Δ and cdc13-1 yeast mutants

    PMID:12154123 PMID:15454530

    Open questions at the time
    • Did not reconstitute telomeric resection biochemically
    • Regulators limiting telomeric resection not identified
  5. 2008 High

    The architecture of DSB resection was unresolved; EXO1 and Sgs1/BLM were defined as parallel long-range resection pathways acting downstream of MRX-Sae2 initiation.

    Evidence Physical resection (Southern) assays and genetic double-mutant epistasis in S. cerevisiae

    PMID:18805091 PMID:18806779

    Open questions at the time
    • Did not establish the biochemical interactions enabling each pathway
    • How initiation hands off to long-range resection unclear
  6. 2008 High

    How resection extent is restrained was unknown; checkpoint-dependent phosphorylation of Exo1 was shown to inhibit its activity as a negative-feedback brake on ssDNA accumulation.

    Evidence MS phosphosite mapping, mutagenesis, and QAOS ssDNA assays under checkpoint-pathway epistasis in yeast

    PMID:18756267

    Open questions at the time
    • Did not identify the direct kinase at each site
    • Mechanism by which phosphorylation inhibits activity unresolved
  7. 2009 Medium

    EXO1's role in human DSB repair was uncertain; it was shown to accumulate at breaks, drive RPA/Rad51 loading, and be ATM-phosphorylated to tune HR.

    Evidence siRNA depletion, foci immunofluorescence, IR-sensitivity and phosphorylation assays in mammalian cells

    PMID:20019063

    Open questions at the time
    • Did not separate catalytic from scaffolding contributions in cells
    • Phosphosites not individually mapped
  8. 2010 High

    Whether EXO1's meiotic functions are separable was unknown; nuclease-dead alleles showed distinct catalytic resection and non-catalytic pro-crossover (Mlh1-Mlh3) roles.

    Evidence Nuclease-dead exo1 alleles with physical resection and double-Holliday-junction assays in yeast meiosis

    PMID:21172664

    Open questions at the time
    • Molecular basis of the non-catalytic crossover role not yet defined
    • Did not identify recruited downstream factors
  9. 2010 High

    The recruitment logic at break ends was unclear; MRX was shown to recruit and stimulate EXO1 while Ku antagonizes its loading, establishing opposing regulators in vitro and in vivo.

    Evidence Exo1 ChIP at DSBs plus in vitro resection with purified yeast proteins; genetic Ku/MRX/Sae2 epistasis

    PMID:20729809 PMID:20834227

    Open questions at the time
    • Did not resolve how MRX physically remodels ends for EXO1
    • Quantitative balance of competing factors in vivo unclear
  10. 2010 High

    EXO1's involvement in lesion processing during NER was unknown; it was shown to enlarge NER intermediates into ssDNA gaps that activate the Mec1 checkpoint.

    Evidence Electron microscopy, DNA combing, and checkpoint-kinase activation assays in non-cycling yeast

    PMID:20932474

    Open questions at the time
    • Did not determine how EXO1 competes with repair synthesis
    • Human relevance of NER-coupled role untested here
  11. 2011 High

    The human resection machinery was undefined biochemically; reconstitution established EXO1-BLM-RPA-MRN and BLM-DNA2-RPA-MRN as two end-resection systems with defined stimulatory interactions.

    Evidence In vitro reconstitution with purified human proteins and interaction studies; Xenopus extract substrate-specificity assays

    PMID:21325134 PMID:21490081

    Open questions at the time
    • Did not define in vivo coordination between the two pathways
    • Stoichiometry and order of factor assembly unresolved
  12. 2011 High

    How meiotic 5'-ends are made accessible was unclear; Mre11 endonucleolytic nicking was shown to license bidirectional resection with EXO1 acting 5'→3' away from the break.

    Evidence Physical 5'-end processing assays with Mre11 and Exo1 nuclease mutants in yeast meiosis

    PMID:22002605

    Open questions at the time
    • Did not address nick recognition by EXO1 directly
    • Coordination of the two opposing nucleases in time unresolved
  13. 2012 Medium

    EXO1's role at mammalian telomeres and in BRCA1/53BP1 resection control was unknown; it was shown to perform extensive telomeric overhang resection and to mediate resection rescue upon 53BP1 loss.

    Evidence In-gel telomere overhang hybridization with mouse knockouts; siRNA epistasis and checkpoint assays in human cells

    PMID:22326273 PMID:22748632

    Open questions at the time
    • Did not reconstitute telomeric CST/POT1b counter-regulation biochemically
    • Cell-cycle control of telomeric EXO1 activity incompletely mapped
  14. 2013 High

    Whether catalytic and structural EXO1 functions are genetically separable in mammals was unknown; a nuclease-dead knockin mouse showed enzymatic activity is specifically required for DSB resection but not MMR/CSR/meiosis.

    Evidence E109K knockin vs Exo1-null mice assessed across MMR, CSR, meiosis, DSB repair, and tumor suppression

    PMID:23754438

    Open questions at the time
    • Did not define the scaffolding partners mediating non-catalytic roles
    • Tissue-specific dependency not fully resolved
  15. 2013 High

    Processivity determinants were unclear; PCNA was shown to load at breaks and confer EXO1 processivity via a direct C-terminal interaction.

    Evidence Co-IP and in vitro resection with purified proteins; Xenopus extract and mammalian cell validation

    PMID:23939618

    Open questions at the time
    • Did not define how PCNA loading is coordinated with end resection initiation
    • Interplay with RPA-mediated turnover not addressed here
  16. 2014 High

    Cell-cycle control of resection was unresolved; CDK1/2 phosphorylation of EXO1 C-terminal sites was shown to promote BRCA1-dependent recruitment and bias repair toward HR.

    Evidence Phosphosite mutagenesis, CDK inhibition, resection/HR-NHEJ reporters, and BRCA1 Co-IP in human cells

    PMID:24705021

    Open questions at the time
    • Direct CDK substrate kinetics not fully characterized
    • How phospho-EXO1 engages BRCA1 structurally unknown
  17. 2015 Medium

    Mechanisms of early recruitment and negative regulation were incomplete; the PIN domain was shown to bind PAR for fast recruitment, while 14-3-3 binding negatively regulates recruitment and limits EXO1-PCNA association.

    Evidence In vitro PAR binding and 14-3-3 Co-IP, live-cell recruitment, variant (R93G) analysis, resection assays

    PMID:25833945 PMID:26400172

    Open questions at the time
    • Did not define how PAR and 14-3-3 inputs are integrated temporally
    • Signals triggering 14-3-3 release unidentified
  18. 2015 Medium

    Additional post-translational control was unknown; EXO1 was shown to be sumoylated via UBC9-PIAS1/4 with SENP6 promoting its stability, linking SUMO to EXO1 turnover.

    Evidence In vitro sumoylation reconstitution, Co-IP, site mapping, chromosomal aberration assays in human cells

    PMID:26083678

    Open questions at the time
    • Coupling of sumoylation to specific ubiquitin ligases not defined
    • Functional consequence at break sites in vivo incompletely resolved
  19. 2015 High

    How Ku blockage and RPA limit resection was unclear; reconstitution showed Ku protects short-tailed ends from Exo1 while RPA can exclude Ku at short ssDNA tails to permit processing.

    Evidence In vitro reconstitution with purified yeast proteins; nuclease protection and binding-competition assays

    PMID:26067273

    Open questions at the time
    • Did not address in vivo kinetics of Ku displacement
    • Role of additional factors (MRX, Sae2) in displacement here limited
  20. 2016 High

    How RPA controls processive resection was unresolved; single-molecule imaging showed EXO1 is intrinsically processive but is actively stripped from DNA by RPA, while SOSS1 supports processivity.

    Evidence Single-molecule fluorescence imaging, domain-mutant analysis, and damage-site recruitment in human cells

    PMID:26884156

    Open questions at the time
    • Did not define how RPA turnover is balanced with productive resection in vivo
    • Structural basis of RPA-mediated stripping unknown
  21. 2016 Medium

    Chromatin inputs to EXO1 recruitment were unclear; CRL4-Wdr70-driven H2B monoubiquitination was shown to limit the resection inhibitor Crb2 and promote Exo1 association at breaks.

    Evidence Exo1 ChIP, histone modification analysis, and genetic epistasis in S. pombe

    PMID:27098497

    Open questions at the time
    • Did not show direct EXO1 reading of the modification
    • Conservation to mammalian H2B marks not tested here
  22. 2017 Medium

    EXO1's role in fork processing and its degradation control were unclear; EXO1 was shown to extend MRE11-initiated reversed-fork resection in BRCA2-deficient cells, and ATR-coupled SCF-mediated ubiquitination degrades EXO1 to cap resection extent.

    Evidence DNA fiber and SQ-motif mutagenesis/ubiquitination assays with HR/NHEJ reporters in human cells

    PMID:28515316 PMID:29038425

    Open questions at the time
    • Specific SCF substrate receptor not fully defined
    • How phospho-degron timing is set during repair unclear
  23. 2018 High

    How EXO1 is targeted to MMR substrates was unresolved; SHIP and MIP peptides in the Exo1 C-terminus were shown to tether it redundantly to Msh2-Msh6 and Mlh1 for MMR.

    Evidence SHIP/MIP mutagenesis with in vitro MMR reconstitution and in vivo mutation-rate assays in yeast

    PMID:30061603

    Open questions at the time
    • Structural details of the peptide-MutS/MutL interfaces not resolved
    • Regulation of these interactions by modification unaddressed
  24. 2018 High

    How resection initiates at Ku-blocked ends was unclear; reconstitution showed a nick provides an entry site for Exo1 (or Sgs1-Dna2) to start long-range resection.

    Evidence Fully reconstituted nick-initiated resection with purified yeast Ku, Exo1, MRX, Sae2, RPA, and Sgs1-Dna2 complex

    PMID:30224356

    Open questions at the time
    • Did not define how the nick is positioned in vivo
    • Choice between Exo1 and Sgs1-Dna2 at the nick not resolved
  25. 2018 Medium

    How MRX potentiates Exo1 beyond recruitment was unclear; MRX was shown to alter DNA end structure to favor Exo1 processing and exclude Ku, with Exo1 itself preventing Ku association.

    Evidence Molecular dynamics simulation, in vivo resection assays, Ku ChIP, and Mre11/exo1 mutant analysis in yeast

    PMID:29925516

    Open questions at the time
    • Simulation-derived end melting not directly visualized structurally
    • Quantitative contribution to in vivo resection rates unclear
  26. 2019 High

    Control of EXO1 at replication forks and in G1 was unknown; AMPK (via CaMKK2/Ca2+) phosphorylates EXO1-S746 to promote 14-3-3 binding and prevent unscheduled fork resection, while RBX1/Cullin1 neddylation degrades EXO1 in G1 to limit HR.

    Evidence In vitro kinase assays, S746A mutagenesis, 14-3-3 Co-IP, fork resection/iPOND, and cell-cycle ubiquitination assays in human cells

    PMID:31053472 PMID:31562368

    Open questions at the time
    • Did not define how distinct kinase inputs are integrated at single forks
    • Substrate-receptor specificity of the G1 ligase not fully mapped
  27. 2020 Medium

    Chromatin docking at stressed forks and at G-quadruplexes was unclear; H4K8ac was shown to recruit EXO1/MRE11 to stalled forks, and EXO1 was shown to resect nascent DNA to allow replication through G-quadruplexes.

    Evidence ChIP-seq, H4K8ac-binding domain mapping, fork degradation/stalling assays and reporters in human cells

    PMID:32232411 PMID:32966758

    Open questions at the time
    • Did not define the EXO1 H4K8ac-binding interface structurally
    • How EXO1 distinguishes productive vs destructive fork processing unclear
  28. 2020 High

    The molecular basis of EXO1's non-catalytic meiotic role was unknown; EXO1 was shown to constitutively bind MutLγ and recruit Cdc5/polo kinase to trigger crossover activity.

    Evidence Reciprocal Co-IP, ChIP of recombination intermediates, and non-catalytic exo1 alleles with cdc5 epistasis in yeast

    PMID:33199619

    Open questions at the time
    • Structural interface for Cdc5 recruitment not defined
    • Whether a mammalian equivalent exists untested here
  29. 2021 High

    The redundancy structure of MMR was incomplete; Rad27 was shown to define an Exo1-independent MMR pathway redundant with Exo1-dependent and Pms1-endonuclease branches, reconstituted in vitro.

    Evidence In vitro MMR reconstitution and genetic epistasis among exo1, rad27, and pms1 alleles in yeast

    PMID:34552065

    Open questions at the time
    • Relative in vivo contribution of each branch in human cells unresolved
    • How the branches are selected at a given mismatch unclear
  30. 2022 Medium

    How reversed forks are protected from EXO1 and then licensed for resection was unclear; KU protects reversed forks, recruits PARP14-MRE11, and MRE11 partial resection releases KU to permit EXO1 long-range resection.

    Evidence DNA fiber, iPOND, proximity ligation, PARP14 inhibition, and epistasis in human cells

    PMID:36030235

    Open questions at the time
    • Direct EXO1-KU competition at forks not reconstituted
    • Order of steps inferred from epistasis rather than real-time observation
  31. 2023 Medium

    How replication-stress ssDNA gaps mature was unclear; MRE11 and EXO1 were shown to extend gaps bidirectionally before MRE11 cleavage converts them to DSBs, with BRCA suppressing the process.

    Evidence DNA fiber, S1-nuclease gap assay, knockdowns, and DSB detection (γH2AX, comet) in human cells

    PMID:37805499

    Open questions at the time
    • Did not define the directionality determinants of each nuclease at gaps
    • Physiological consequence of gap-to-DSB conversion incompletely mapped
  32. 2024 Medium

    The basis of EXO1 dependency in BRCA-deficient tumors was unknown; EXO1 was shown to be essential specifically in BRCA1-deficient cells through its requirement in single-strand annealing repair.

    Evidence CRISPR viability screen, siRNA depletion, PAR/γH2AX foci, SSA reporter, and tumor genomic-scar analysis in human cells

    PMID:38266640

    Open questions at the time
    • Mechanistic role of EXO1 within SSA not biochemically reconstituted
    • Whether dependency holds across BRCA1-mutant tumor contexts in vivo untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many competing recruitment (MRX/MRN, PCNA, PAR, SOSS1, chromatin marks) and inhibitory (Ku, RPA, 14-3-3, phosphorylation, degradation) inputs are quantitatively integrated to set resection extent at a single lesion in real time remains unresolved.
  • No high-resolution structure of EXO1 bound to DNA with regulatory partners
  • Integration of cell-cycle, chromatin, and post-translational inputs not modeled quantitatively

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3 GO:0016787 hydrolase activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3
Partners
14-3-3BRCA1MLH1MLH3MRE11MSH2PCNARPA

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 S. cerevisiae Exo1 is a double-stranded DNA-specific 5'→3' exonuclease that interacts with MSH2 (both S. cerevisiae and human MSH2) as shown by two-hybrid and co-immunoprecipitation experiments; exo1 mutants show a mutator phenotype epistatic with the MSH2-dependent mismatch repair pathway, and overexpression of EXO1 suppresses the temperature-sensitive and mutator phenotypes of rad27 mutants. Two-hybrid screen, co-immunoprecipitation, epistasis analysis, mutator phenotype assay, suppression genetics Proceedings of the National Academy of Sciences of the United States of America High 9207118
1998 Human EXO1 (HEX1) encodes a 5'→3' exonuclease that is a member of the Rad2 nuclease family; recombinant human Exo1 exhibits 5'→3' exonuclease activity in vitro, and the human protein can functionally complement the mutator phenotype of S. cerevisiae rad27 mutants, indicating functional conservation. In vitro nuclease assay with recombinant protein, yeast complementation Nucleic acids research High 9685493 9823303
1999 Exo1 (5'→3') and the 3'→5' proofreading exonucleases of DNA polymerase epsilon and delta play major roles in postreplication mismatch repair in S. cerevisiae; the mutation rate in an exo1 pol3-01 double mutant was comparable to that in an msh2 pol3-01 mutant, indicating Exo1 participates directly in mismatch repair. Genetic epistasis analysis, mutation rate measurement using homonucleotide run reporters Molecular and cellular biology Medium 10022887
2000 In S. cerevisiae, Exo1 promotes meiotic DSB resection (5'→3') and meiotic crossing over but not gene conversion; exo1 mutation reduces processing of DSBs and crossing-over frequency; Exo1 and Mre11 function independently in DSB processing as shown by additive sensitivity of exo1 mre11 double mutants. Genetic analysis (single and double mutants), physical DSB processing assay, meiotic crossover frequency measurement Molecular biology of the cell Medium 10888664
2001 EXO1 plays a structural (non-catalytic) role in stabilizing mismatch repair protein complexes containing MLH1, PMS1, MSH2, MSH3, PCNA, and POL32, in addition to its catalytic role; exo1-dependent mutator mutations were identified in these MMR genes and exhibit unlinked noncomplementation and high-copy suppression patterns consistent with EXO1 stabilizing multiprotein MMR complexes. Genetic screen for exo1-dependent mutator mutations, epistasis analysis, non-complementation tests, high-copy suppression Molecular and cellular biology Medium 11438669
2002 Human Exo1 active-site residues D78, D173, and D225 are critical for nuclease function; the 5'-phosphate group stimulates Exo1 degradation ~10-fold; Exo1 binds predominantly along the minor groove of flap DNA downstream of the junction as shown by hydroxyl radical footprinting; an abasic lesion impedes Exo1 nucleolytic degradation. Site-directed mutagenesis, in vitro nuclease assay, hydroxyl radical footprinting Nucleic acids research High 11842105
2002 Exo1 generates ssDNA at subtelomeric regions of yku70Δ mutants, and this ssDNA accumulation is required for cell cycle arrest; Exo1 is required for both ssDNA generation and checkpoint arrest at dysfunctional telomeres, while MRE11 is not required for this ssDNA generation. Genetic analysis (double mutants), quantitative ssDNA detection (QAOS), cell cycle arrest assay Genes & development Medium 12154123
2003 In S. pombe, Exo1 is the alternative nuclease targeting DSB ends in the absence of the Rad50 complex; Ku heterodimer inhibits DSB processing by Exo1 when the Rad50 complex is absent; Exo1 is not the nuclease acting on telomere ends in this context. Genetic epistasis (rad50, pku70, exo1 deletion combinations), MMS sensitivity assay, telomere overhang analysis Molecular and cellular biology Medium 12861005
2004 Exo1 in S. cerevisiae generates ssDNA at uncapped telomeres (cdc13-1 mutants) and is required particularly for ssDNA generation in subtelomeric X repeats and internal single-copy sequences; Rad24 and Exo1 regulate different nuclease activities at uncapped telomeres. Genetic analysis (cdc13-1 and exo1 mutants), quantitative ssDNA detection (QAOS), cell cycle arrest assay Genetics Medium 15454530
2005 Exo1 exonuclease is recruited to stalled replication forks in HU-treated rad53 checkpoint-defective yeast cells and generates ssDNA intermediates that counteract reversed fork accumulation; Exo1 thus processes collapsed forks analogously to E. coli RecJ nuclease. 2D gel electrophoresis, electron microscopy with psoralen crosslinking, genetic analysis Molecular cell High 15629726
2005 EXO1 functions in the MMS2 error-free branch of the post-replication repair (PRR) pathway independently of its role in mismatch repair; a domain of Exo1 required for PRR is distinct from the Mlh1-interacting domain required for MMR; Exo1 plays both structural and catalytic roles during MMR. Genetic epistasis (exo1 alleles, mms2 mutants), point mutant analysis separating MMR and PRR functions, mutator phenotype assay DNA repair Medium 17602897
2007 EXO1 interacts with the Srs2 helicase; Srs2 unwinds DNA from the 5' side of a nick at a ribonucleoside monophosphate residue and enhances Exo1 nuclease activity to generate a DNA gap for repair, defining a Srs2-Exo1 pathway of nick processing to tolerate ribonucleoside monophosphates in DNA. Genetic analysis, in vitro biochemical assay (Srs2-Exo1 interaction and activity), epistasis with RNase H2 mutants Nature Medium 24896181
2008 In S. cerevisiae DSB repair, Exo1 nuclease and Sgs1 helicase function in alternative long-range resection pathways downstream of Mre11-Rad50-Xrs2/Sae2-mediated initiation; in exo1Δ sgs1Δ double mutants, only short partially resected intermediates accumulate that are poor substrates for homologous recombination; Sae2 is required for the initial processing step. Physical DSB resection assay (Southern blot), genetic double mutant analysis, HR efficiency measurement Nature High 18805091 18806779
2008 Exo1 in S. cerevisiae is phosphorylated at serines S372, S567, S587, and S692 in a checkpoint-dependent manner (requiring Rad24, Rad17, Rad9, Rad53, and Mec1) following telomere uncapping or DNA damage; this phosphorylation appears to inhibit Exo1 activity, constituting a negative feedback loop to limit ssDNA accumulation. Mass spectrometry phosphorylation site identification, site-directed mutagenesis, quantitative ssDNA assay, genetic epistasis The EMBO journal High 18756267
2009 Human Exo1 accumulates rapidly at DNA DSBs, is required for RPA and Rad51 recruitment to DSB sites (indicating a role in ssDNA generation), and is phosphorylated by ATM following DSB resection to regulate its activity and allow optimal Rad51 loading and HR completion; Exo1 depletion causes chromosomal instability and IR hypersensitivity. siRNA depletion, immunofluorescence foci analysis, IR sensitivity assay, phosphorylation detection Nucleic acids research Medium 20019063
2010 During meiosis, Exo1 has two temporally and biochemically distinct functions: (1) catalytic DSB resection generating long 3' ssDNA tails, and (2) a non-nuclease structural role promoting resolution of double Holliday junctions into crossovers through interaction with Mlh1-Mlh3; dHJs form at wild-type levels in exo1Δ mutants, showing the resection and pro-crossover functions are separable. Physical DSB resection assay, double Holliday junction detection, nuclease-dead exo1 alleles, genetic analysis of crossover frequency Molecular cell High 21172664
2010 MRX complex recruits Exo1 to DSB ends and stimulates its recruitment, while Ku antagonizes Exo1 binding; in vitro resection assays with purified enzymes show Ku and MRX regulate Exo1 nuclease activity in opposing ways; efficient Exo1 loading does not require Sae2 or Mre11 nuclease activities. ChIP of Exo1 at DSBs, in vitro resection assay with purified proteins, genetic analysis The EMBO journal High 20834227
2010 In the absence of Ku, the MRX complex requirement for DSB resection is bypassed and resection is executed by Exo1 alone; both Exo1 and Sgs1 resection pathways contribute to DSB processing in the absence of Ku and Sae2. Genetic epistasis (ku70Δ, exo1Δ, sgs1Δ, sae2Δ combinations), physical resection assay The EMBO journal Medium 20729809
2010 During NER of UV lesions in non-cycling yeast cells, Exo1 competes with repair DNA synthesis to process NER intermediates, generating extended ssDNA gaps detectable by electron microscopy that drive Mec1 kinase (checkpoint) activation. Electron microscopy, DNA combing, checkpoint kinase activation assay, genetic analysis Molecular cell High 20932474
2011 Human BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two biochemically reconstituted DSB end resection machineries; BLM increases EXO1's affinity for DNA ends; MRN recruits and enhances EXO1 processivity; RPA stimulates EXO1 resection in the EXO1 pathway. In vitro reconstitution with purified human proteins, nuclease assay, physical interaction studies Genes & development High 21325134
2011 In S. cerevisiae meiosis, Mre11 endonuclease nicks the strand to be resected up to 300 nt from the 5'-DSB terminus, enabling bidirectional resection: Exo1 resects 5'→3' away from the DSB, and Mre11 exonuclease resects 3'→5' toward the DSB end; both exonuclease activities are required for efficient DSB repair. Physical assays for 5'-end processing in vivo, Mre11 and Exo1 nuclease mutants, S. cerevisiae meiosis Nature High 22002605
2011 Xenopus EXO1 displays strong 5'→3' dsDNA exonuclease activity but no significant ssDNA exonuclease activity; xEXO1 depletion inhibits 5'-strand resection; xEXO1 acts directly on dsDNA in parallel with xDNA2 (which acts on ssDNA unwound by xWRN); both initiation and extension stages of resection require xEXO1. Xenopus egg extract reconstitution, protein depletion, in vitro resection assay, substrate specificity testing Nucleic acids research High 21490081
2012 At mammalian telomeres, Exo1 extensively resects both leading- and lagging-end telomeres generating transient long 3' overhangs in S/G2; Apollo initiates 3' overhang formation at leading-end telomeres; POT1b blocks hyperresection; CST/AAF bound to POT1b shortens Exo1-generated overhangs through fill-in synthesis. In-gel hybridization for telomere overhangs, cell cycle fractionation, mouse genetic knockouts, live-cell analysis Cell High 22748632
2012 Human Exo1 plays a predominant role in DSB end resection in vivo; Exo1 recruitment to DSBs is inhibited by Ku80; the restoration of resection in BRCA1-deficient cells upon 53BP1 depletion is dependent on Exo1; Exo1-mediated resection facilitates a transition from ATM- to ATR-mediated checkpoint signaling. siRNA depletion, RPA/BrdU/ssDNA foci analysis, epistasis by double-knockdown, checkpoint kinase phosphorylation assay DNA repair Medium 22326273
2012 The SOSS1 complex (containing SSB1) promotes Exo1 interaction with dsDNA ends and stimulates its activity independently of MRN in vitro; both MRN and SOSS1 mitigate the inhibitory effect of Ku70/80 on Exo1 activity in vitro. In vitro nuclease assay with purified proteins, single-molecule and ensemble DNA binding studies The EMBO journal Medium 23178594
2013 PCNA loads onto DSBs and promotes Exo1 damage association through direct interaction with Exo1's C-terminal domain; PCNA confers processivity to Exo1 during resection; this role was demonstrated in mammalian cells, Xenopus nuclear extracts, and with purified proteins. Co-immunoprecipitation, in vitro resection assay with purified proteins, Xenopus extract, mammalian cell experiments Nucleic acids research High 23939618
2013 Mammalian EXO1 has separable structural and catalytic functions in vivo: the exonuclease-deficient E109K knockin retains MMR activity and normal class switch recombination and meiosis, but both Exo1-null and E109K mice show defects in DSB repair via end resection, chromosomal stability, and tumor suppression, indicating the enzymatic function is specifically required for DSB repair. Knockin mouse generation (E109K), comparison with Exo1-null mice, MMR assay, CSR assay, meiosis analysis, DSB repair assay Proceedings of the National Academy of Sciences of the United States of America High 23754438
2014 CDK1/2 phosphorylate EXO1 at four C-terminal S/TP sites during S/G2 phase; phosphorylation of EXO1 augments its recruitment to DNA breaks via interactions with BRCA1; impairment of phosphorylation attenuates resection and HR while augmenting NHEJ; phospho-mimetic EXO1 is proficient in resection even after CDK inhibition; mutation of cyclin-binding sites attenuates CDK binding and EXO1 phosphorylation. Site-directed mutagenesis of phospho-sites, CDK inhibitor treatment, resection assay (BrdU/RPA foci), HR/NHEJ reporter assay, co-immunoprecipitation with BRCA1 Nature communications High 24705021
2014 PCNA and Msh2-Msh6 activate the Mlh1-Pms1 endonuclease pathway required for Exo1-independent MMR; specific PCNA mutations at three structural sites impair either trimerization/Msh2-Msh6 binding or Mlh1-Pms1 endonuclease activation, revealing PCNA's central role in the Exo1-independent MMR pathway. Genetic screen for PCNA mutations, biochemical analysis of PCNA mutant functions, epistasis with exo1 and msh6 mutations Molecular cell Medium 24981171
2015 The PIN domain of EXO1 recognizes poly(ADP-ribose) (PAR) both in vitro and in vivo, and this interaction mediates rapid early recruitment of EXO1 to DNA damage sites; the R93G variant abolishes PAR binding and early recruitment; PAR-mediated fast recruitment of EXO1 facilitates early DNA end resection. In vitro PAR binding assay, co-immunoprecipitation, live-cell recruitment assay, variant analysis (R93G) Nucleic acids research Medium 26400172
2015 14-3-3 proteins interact with a central region of Exo1 and negatively regulate Exo1 damage recruitment and subsequent resection; 14-3-3 limits Exo1-PCNA association; disruption of Exo1-14-3-3 interaction elevates DNA damage sensitivity. Co-immunoprecipitation, in vivo damage foci assay, resection assay, genetic interaction with PCNA binding mutants The Journal of biological chemistry Medium 25833945
2015 EXO1 is sumoylated in human cells via UBC9-PIAS1/PIAS4 (conserved as Ubc9-Siz1/Siz2 in yeast); sumoylation affects EXO1 ubiquitylation and protein stability; EXO1 physically interacts with the SUMO-protease SENP6 which promotes EXO1 stability; sumoylation-deficient EXO1 rescues DNA damage-induced chromosomal aberrations. Co-immunoprecipitation, in vitro sumoylation reconstitution, site mapping by mutagenesis, chromosomal aberration assay Cell cycle Medium 26083678
2015 In a reconstituted yeast system, Ku protects blunt-ended DNA and partially resected DNA ends (≥40 nt ssDNA tail) against Exo1; RPA can exclude Ku from partially resected structures with 22-nt ssDNA tails, restoring Exo1 processing; at 40-nt tails, Ku remains stable and RPA occupies the ssDNA region simultaneously. In vitro reconstitution with purified yeast proteins, nuclease protection assay, binding competition assay The Journal of biological chemistry High 26067273
2016 Human and yeast Exo1 are processive nucleases on their own; RPA rapidly strips Exo1 from DNA (requiring ≥3 RPA ssDNA-binding domains), limiting resection; ablation of RPA in human cells increases Exo1 recruitment to damage sites; the SOSS1 (SSB1-containing) complex supports processive resection by Exo1 in contrast to RPA. Single-molecule fluorescence imaging, quantitative cell biology (damage site recruitment), protein domain mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 26884156
2016 CRL4-Wdr70 E3 ligase stimulates H2B lysine 119 monoubiquitination (uH2B) at DSBs in S. pombe; uH2B loss results in increased loading of the resection inhibitor Crb2 (53BP1 ortholog), decreased Exo1 association, and delayed resection; Wdr70 is dispensable for resection upon Crb2 loss, placing the histone modification pathway upstream of Exo1 recruitment. ChIP of Exo1 at DSBs, genetic epistasis (wdr70Δ, crb2Δ combinations), histone modification analysis, resection assay Nature communications Medium 27098497
2017 In BRCA2-deficient cells, CtIP initiates MRE11-dependent degradation of reversed replication fork regressed arms, which is then extended by EXO1; this EXO1-extended resection establishes the substrate for MUS81, whose cleavage promotes POLD3-dependent fork rescue. DNA fiber assay, siRNA epistasis, proximity ligation assay, genetic analysis Nature communications Medium 29038425
2017 EXO1 is rapidly degraded by the ubiquitin-proteasome system after DSB induction via ATR-mediated phosphorylation of SQ motifs that target EXO1 for SCF-family ubiquitin ligase-mediated ubiquitination; degradation-resistant EXO1 causes hyper-resection that attenuates both NHEJ and HR, demonstrating that EXO1 degradation limits resection extent for accurate DSB repair. Proteasome inhibitor treatment, SQ motif mutagenesis, ubiquitination assay, HR/NHEJ reporter assay, resection assay The Journal of biological chemistry High 28515316
2018 The unstructured C-terminal domain of S. cerevisiae Exo1 contains two MutS homolog 2 (Msh2)-interacting peptide (SHIP) boxes downstream of the Mlh1-interacting peptide (MIP) box; these three sites are redundant for Exo1-dependent MMR in vivo; wild-type but not mutant SHIP peptides eliminated Exo1-dependent MMR in vitro; Exo1 is recruited to MMR by being tethered to the Msh2-Msh6 complex. Mutagenesis of SHIP/MIP motifs, in vitro MMR reconstitution, in vivo mutation rate assay, protein interaction studies Nature structural & molecular biology High 30061603
2018 A nick at Ku-blocked DSB ends serves as an entry site for Exo1 (or Sgs1-Dna2) to initiate long-range 5'→3' resection; Sgs1 unwinds duplex DNA harboring a nick in a manner dependent on RPA; this was demonstrated in fully reconstituted systems with purified yeast proteins. In vitro reconstitution with purified proteins (Ku, Exo1, MRX, Sae2, RPA, Sgs1-Top3-Rmi1-Dna2), nick-initiated resection assay The Journal of biological chemistry High 30224356
2018 The MRX complex promotes Exo1 resection activity by altering DNA end structure; the Mre11-R10T variant that causes altered capping domain orientation leads to persistent melting of dsDNA ends, potentiating Exo1-mediated processing and decreasing Ku association at DSBs; Exo1 directly prevents Ku from associating with DSBs. Molecular dynamics simulation, in vivo resection assay, Ku ChIP, exo1 genetic analysis, Mre11 mutant analysis The EMBO journal Medium 29925516
2019 Replication stress elevates intracellular Ca2+ concentration, activating CaMKK2 and downstream AMPK, which directly phosphorylates EXO1 at serine 746; this phosphorylation promotes 14-3-3 binding and inhibits EXO1 recruitment to stressed replication forks, preventing unscheduled fork resection; disruption causes excessive ssDNA, chromosomal instability, and replication stress hypersensitivity. In vitro kinase assay (AMPK phosphorylating EXO1), mutagenesis (S746A), 14-3-3 co-IP, Ca2+ imaging, fork resection assay (iPOND/fiber), chromosomal instability assay Molecular cell High 31053472
2019 RBX1-promoted neddylation of Cullin1 drives ubiquitination-mediated degradation of EXO1 specifically in G1 phase, limiting HR repair; RBX1 expression is elevated in G1 through DNA-PKcs autophosphorylation at S2056; RBX1 knockdown increased EXO1 expression and DSB end resection in G1. Western blot of EXO1 levels across cell cycle, RBX1 siRNA, DNA-PKcs inhibition, foci assay (RPA32, BrdU, RAD51), ubiquitination assay Cell death and differentiation Medium 31562368
2020 PCAF histone acetyltransferase promotes H4K8 acetylation at stalled replication forks in BRCA-deficient cells; H4K8ac serves as a docking site for MRE11 and EXO1, which contain an H4K8ac-binding domain required for their fork recruitment; ATR phosphorylates PCAF at S264 to limit its activity at stalled forks. ChIP-seq, domain mapping (H4K8ac-binding), siRNA depletion, fork degradation assay (fiber), ATR inhibitor treatment Molecular cell Medium 32966758
2020 Exo1 constitutively interacts with MutLγ (Mlh1-Mlh3); upon commitment to meiotic crossover repair, MutLγ-Exo1 associates with recombination intermediates, followed by direct Cdc5 (polo kinase) recruitment that triggers MutLγ crossover activity; Exo1 provides a non-catalytic role as a central coordinator recruiting polo kinase to crossover sites. Co-immunoprecipitation (Exo1-MutLγ constitutive interaction), ChIP of recombination intermediates, genetic analysis of exo1 non-catalytic alleles, epistasis with cdc5 Proceedings of the National Academy of Sciences of the United States of America High 33199619
2020 EXO1 plays a key role in resolution of and replication through telomeric G-quadruplex structures; EXO1 resects nascent DNA proximal to stalled G-quadruplexes to facilitate fork progression; in the absence of EXO1, forks collapse at G-quadruplexes and are repaired via error-prone end joining, causing genomic instability and telomere dysfunction. EXO1 depletion, fork stalling assay, G-quadruplex stabilizer treatment, NHEJ/HR reporter, telomere function assay Nucleic acids research Medium 32232411
2021 Rad27 defines an Exo1-independent eukaryotic MMR pathway in S. cerevisiae that is redundant with at least two other MMR pathways (Exo1-dependent and Pms1-endonuclease-dependent); a Rad27- and Msh2-Msh6-dependent MMR reaction was reconstituted in vitro using purified MMR proteins. In vitro MMR reconstitution with purified proteins, genetic analysis of exo1Δ440-702 and rad27Δ and pms1-A99V combinations, mutation rate assay Nature communications High 34552065
2022 The KU complex binds reversed replication forks and protects them against EXO1-catalyzed degradation; KU recruits the PARP14-MRE11 complex to reversed forks, where PARP14 mediates (via its catalytic ADP-ribosyltransferase activity) MRE11 engagement; MRE11 initiates partial resection to release KU, allowing long-range resection by EXO1. DNA fiber assay, siRNA depletion, iPOND, proximity ligation assay, PARP14 inhibitor treatment, epistasis Nature communications Medium 36030235
2023 Replication stress-induced ssDNA gaps are extended bidirectionally: MRE11 extends gaps 3'→5' and EXO1 extends them 5'→3'; subsequently, MRE11 endonuclease cleaves the parental strand at the ssDNA gap generating a DSB; this processing is suppressed by the BRCA pathway. DNA fiber assay, S1 nuclease-based gap assay, genetic knockdown (MRE11, EXO1, BRCA), DSB detection (γH2AX, comet assay) Nature communications Medium 37805499
2024 EXO1 is essential for BRCA1-deficient cells: EXO1 deficiency generates PAR-decorated DNA lesions during S phase associated with unresolved DSBs in BRCA1-deficient (but not wild-type or BRCA2-deficient) cells due to impaired single-strand annealing (SSA) repair on top of HR defect; BRCA2-deficient cells retain SSA activity without EXO1 and tolerate EXO1 loss. CRISPR-based cell viability screen, siRNA depletion, PAR foci analysis, DSB foci (γH2AX), SSA reporter assay, genomic scar analysis in tumor data Molecular cell Medium 38266640

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 874 18805091
2008 Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 834 18806779
2011 BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes & development 590 21325134
2011 Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1. Nature 364 22002605
2017 MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. Nature communications 346 29038425
1997 Identification and characterization of Saccharomyces cerevisiae EXO1, a gene encoding an exonuclease that interacts with MSH2. Proceedings of the National Academy of Sciences of the United States of America 331 9207118
2002 EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes & development 262 12154123
2010 Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2. The EMBO journal 252 20729809
2012 Telomeric 3' overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell 250 22748632
2005 Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells. Molecular cell 236 15629726
2010 Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions. Molecular cell 204 21172664
1992 Exo1 and Exo2 proteins stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells. Nature 198 1538762
2000 Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae. Molecular biology of the cell 185 10888664
2010 Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks. The EMBO journal 181 20834227
1999 The 3'-->5' exonucleases of DNA polymerases delta and epsilon and the 5'-->3' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. Molecular and cellular biology 178 10022887
2004 EXO1-A multi-tasking eukaryotic nuclease. DNA repair 177 15474417
2001 exo1-Dependent mutator mutations: model system for studying functional interactions in mismatch repair. Molecular and cellular biology 177 11438669
2009 Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks. Nucleic acids research 146 20019063
2001 Overlapping functions of the Saccharomyces cerevisiae Mre11, Exo1 and Rad27 nucleases in DNA metabolism. Genetics 145 11779786
2014 Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice. Nature communications 144 24705021
2008 Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. The EMBO journal 137 18756267
1998 Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination. Cancer research 126 9823303
2003 Competition between the Rad50 complex and the Ku heterodimer reveals a role for Exo1 in processing double-strand breaks but not telomeres. Molecular and cellular biology 124 12861005
2001 Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms. Gastroenterology 119 11375940
2012 Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions. DNA repair 114 22326273
2000 Hex-1, a gene unique to filamentous fungi, encodes the major protein of the Woronin body and functions as a plug for septal pores. Fungal genetics and biology : FG & B 103 11273682
2010 Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation. Molecular cell 102 20932474
2004 Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 102 15454530
1998 Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1. Nucleic acids research 100 9685493
2014 PCNA and Msh2-Msh6 activate an Mlh1-Pms1 endonuclease pathway required for Exo1-independent mismatch repair. Molecular cell 89 24981171
1992 Activation of protein kinase C by the 14-3-3 proteins homologous with Exo1 protein that stimulates calcium-dependent exocytosis. FEBS letters 87 1499718
2002 Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase). Genetics 84 11805044
2012 DNA2 and EXO1 in replication-coupled, homology-directed repair and in the interplay between HDR and the FA/BRCA network. Cell cycle (Georgetown, Tex.) 81 22987153
2004 EXO1 contributes to telomere maintenance in both telomerase-proficient and telomerase-deficient Saccharomyces cerevisiae. Genetics 81 15126387
2016 Single-molecule imaging reveals the mechanism of Exo1 regulation by single-stranded DNA binding proteins. Proceedings of the National Academy of Sciences of the United States of America 79 26884156
2010 Sgs1 and exo1 redundantly inhibit break-induced replication and de novo telomere addition at broken chromosome ends. PLoS genetics 78 20523895
2019 Ca2+-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection. Molecular cell 76 31053472
2014 Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms. Nature 72 24896181
1992 Interaction between protein kinase C and Exo1 (14-3-3 protein) and its relevance to exocytosis in permeabilized adrenal chromaffin cells. The Biochemical journal 71 1417740
2015 The WRN exonuclease domain protects nascent strands from pathological MRE11/EXO1-dependent degradation. Nucleic acids research 70 26275776
2014 FOXM1 modulates cisplatin sensitivity by regulating EXO1 in ovarian cancer. PloS one 70 24824601
2013 PCNA promotes processive DNA end resection by Exo1. Nucleic acids research 69 23939618
2012 The SOSS1 single-stranded DNA binding complex promotes DNA end resection in concert with Exo1. The EMBO journal 69 23178594
1994 Molecular cloning and expression of the Candida albicans beta-N-acetylglucosaminidase (HEX1) gene. Journal of bacteriology 68 8169213
2003 A HEX-1 crystal lattice required for Woronin body function in Neurospora crassa. Nature structural biology 66 12640443
2010 Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping. The EMBO journal 65 21045806
2005 DNA interstrand cross-link repair in the Saccharomyces cerevisiae cell cycle: overlapping roles for PSO2 (SNM1) with MutS factors and EXO1 during S phase. Molecular and cellular biology 64 15743825
2002 Molecular interactions of human Exo1 with DNA. Nucleic acids research 62 11842105
2000 EXO1 and MSH6 are high-copy suppressors of conditional mutations in the MSH2 mismatch repair gene of Saccharomyces cerevisiae. Genetics 62 10835383
2020 PCAF-Mediated Histone Acetylation Promotes Replication Fork Degradation by MRE11 and EXO1 in BRCA-Deficient Cells. Molecular cell 60 32966758
2017 DNA-damage-induced degradation of EXO1 exonuclease limits DNA end resection to ensure accurate DNA repair. The Journal of biological chemistry 60 28515316
2000 EXO1 and MSH4 differentially affect crossing-over and segregation. Chromosoma 60 10855499
2018 Human Exonuclease 1 (EXO1) Regulatory Functions in DNA Replication with Putative Roles in Cancer. International journal of molecular sciences 58 30585186
2013 Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes. Proceedings of the National Academy of Sciences of the United States of America 57 23754438
1993 The Saccharomyces cerevisiae SPR1 gene encodes a sporulation-specific exo-1,3-beta-glucanase which contributes to ascospore thermoresistance. Journal of bacteriology 53 8419289
2007 A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair. DNA repair 51 17602897
2003 EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer. Cancer research 50 12517792
2018 MutLγ promotes repeat expansion in a Fragile X mouse model while EXO1 is protective. PLoS genetics 49 30312299
2015 The PIN domain of EXO1 recognizes poly(ADP-ribose) in DNA damage response. Nucleic acids research 49 26400172
2015 Sumoylation regulates EXO1 stability and processing of DNA damage. Cell cycle (Georgetown, Tex.) 45 26083678
2009 A functional EXO1 promoter variant is associated with prolonged life expectancy in centenarians. Mechanisms of ageing and development 44 19698732
2009 Association of genetic polymorphisms of EXO1 gene with risk of breast cancer in Taiwan. Anticancer research 44 19846925
2015 Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines. Genes to cells : devoted to molecular & cellular mechanisms 43 26525166
2022 The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1. Nature communications 41 36030235
2018 Identification of Exo1-Msh2 interaction motifs in DNA mismatch repair and new Msh2-binding partners. Nature structural & molecular biology 41 30061603
2023 Multi-step processing of replication stress-derived nascent strand DNA gaps by MRE11 and EXO1 nucleases. Nature communications 40 37805499
2014 The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic acids research 40 25122752
2021 BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression. Scientific reports 39 33637776
2020 EXO1: A tightly regulated nuclease. DNA repair 39 33087266
2013 The HEX1 gene of Fusarium graminearum is required for fungal asexual reproduction and pathogenesis and for efficient viral RNA accumulation of Fusarium graminearum virus 1. Journal of virology 39 23864619
2009 Lung cancer susceptibility and genetic polymorphisms of Exo1 gene in Taiwan. Anticancer research 38 19331228
2015 Human exonuclease 1 (EXO1) activity characterization and its function on flap structures. Bioscience reports 37 26182368
2010 Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS genetics 37 20808892
2009 Single-nucleotide polymorphism of the Exo1 gene: association with gastric cancer susceptibility and interaction with smoking in Taiwan. The Chinese journal of physiology 37 20337148
2004 Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population. Carcinogenesis 37 15550454
2015 Interplay between Ku and Replication Protein A in the Restriction of Exo1-mediated DNA Break End Resection. The Journal of biological chemistry 36 26067273
2009 Interaction of Exo1 genotypes and smoking habit in oral cancer in Taiwan. Oral oncology 36 19515603
2008 Potentially functional polymorphisms of EXO1 and risk of lung cancer in a Chinese population: A case-control analysis. Lung cancer (Amsterdam, Netherlands) 36 18079015
2019 RBX1 prompts degradation of EXO1 to limit the homologous recombination pathway of DNA double-strand break repair in G1 phase. Cell death and differentiation 35 31562368
2016 CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection. Nature communications 35 27098497
2010 Extensive DNA end processing by exo1 and sgs1 inhibits break-induced replication. PLoS genetics 35 20628570
2020 Exo1 recruits Cdc5 polo kinase to MutLγ to ensure efficient meiotic crossover formation. Proceedings of the National Academy of Sciences of the United States of America 34 33199619
2020 EXO1 resection at G-quadruplex structures facilitates resolution and replication. Nucleic acids research 33 32232411
2020 MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women. Aging 33 32454462
2020 Variants in Homologous Recombination Genes EXO1 and RAD51 Related with Premature Ovarian Insufficiency. The Journal of clinical endocrinology and metabolism 32 32772095
2018 Coordinated Activity of Y Family TLS Polymerases and EXO1 Protects Non-S Phase Cells from UV-Induced Cytotoxic Lesions. Molecular cell 32 29551515
2020 Exonuclease 1 (Exo1) Participates in Mammalian Non-Homologous End Joining and Contributes to Drug Resistance in Ovarian Cancer. Medical science monitor : international medical journal of experimental and clinical research 31 32167078
2011 Mismatch repair proteins MSH2, MLH1, and EXO1 are important for class-switch recombination events occurring in B cells that lack nonhomologous end joining. Journal of immunology (Baltimore, Md. : 1950) 31 21242524
2018 The MRX complex regulates Exo1 resection activity by altering DNA end structure. The EMBO journal 29 29925516
2007 Tumor progression in Apc(1638N) mice with Exo1 and Fen1 deficiencies. Oncogene 29 17452984
2024 EXO1 protects BRCA1-deficient cells against toxic DNA lesions. Molecular cell 27 38266640
2015 14-3-3 proteins restrain the Exo1 nuclease to prevent overresection. The Journal of biological chemistry 26 25833945
2023 A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene. Nature communications 25 36693839
1998 Schizosaccharomyces pombe exo1 is involved in the same mismatch repair pathway as msh2 and pms1. Current genetics 25 9871115
2024 EXO1/P53/SREBP1 axis-regulated lipid metabolism promotes prostate cancer progression. Journal of translational medicine 24 38279172
2012 Exonuclease 1 (EXO1) gene variation and melanoma risk. DNA repair 24 22230721
2004 Isolation, characterization and expression of the hex1 gene from Trichoderma reesei. Gene 24 15094199
2021 Rad27 and Exo1 function in different excision pathways for mismatch repair in Saccharomyces cerevisiae. Nature communications 23 34552065
2018 A DNA nick at Ku-blocked double-strand break ends serves as an entry site for exonuclease 1 (Exo1) or Sgs1-Dna2 in long-range DNA end resection. The Journal of biological chemistry 23 30224356
2011 Mechanistic analysis of Xenopus EXO1's function in 5'-strand resection at DNA double-strand breaks. Nucleic acids research 23 21490081

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