Affinage

ATAD5

ATPase family AAA domain-containing protein 5 · UniProt Q96QE3

Length
1844 aa
Mass
207.6 kDa
Annotated
2026-06-09
54 papers in source corpus 38 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATAD5 (yeast Elg1) is the major subunit of an RFC-like clamp-unloader complex (ATAD5/Elg1-RLC) that maintains genome stability by enforcing the timely removal of the PCNA sliding clamp from chromatin during and after DNA replication (PMID:12912927, PMID:13678589, PMID:12909721, PMID:23277426, PMID:26212319). Unlike the clamp-loading RFC complexes, ATAD5-RLC is a dedicated PCNA unloader: cryo-EM structures reveal unique 'locking loops' and a 'plug' domain that fill the DNA-binding chamber, restricting the complex to unloading and allowing it to remove PCNA even from covalently closed DNA via an ATP-binding (non-hydrolysis-dependent) mechanism distinct from loading (PMID:38871854, PMID:38427736). In vitro reconstitution with purified complex and in Xenopus extracts established that ATAD5/Elg1-RLC directly unloads both unmodified and SUMOylated PCNA and provides the dominant cellular unloading activity, with Okazaki fragment ligation serving as the genome-wide trigger for unloading behind replication forks (PMID:23499004, PMID:26212319, PMID:38141767). Beyond its core enzymatic role, the ATAD5 N-terminus is a scaffold that recruits the USP1-UAF1 deubiquitinase (and USP7/USP11) to deubiquitinate DNA-loaded ubiquitinated PCNA prior to its release (PMID:20147293, PMID:39145935), and recruits RNA helicases (DDX1, DDX5, DDX21, DHX9) to forks to resolve and suppress R-loops (PMID:32542338). Through this control of PCNA residence time, ATAD5 governs replication factory lifespan (PMID:23277426), mismatch repair (PMID:31114918), replication fork restart and RAD51 recruitment at stalled forks (PMID:31844045), short-range DSB end resection (PMID:37739427), sister chromatid cohesion (PMID:19430531, PMID:19262753), and the DNA damage checkpoint (PMID:31186330); failure to clear PCNA—particularly its retention into G2/M—is the principal source of genome instability in its absence (PMID:27373149). Mouse Atad5 haploinsufficiency causes defective PCNA deubiquitination and tumor predisposition, defining its in vivo tumor-suppressor function (PMID:21901109).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2003 High

    Established that ELG1/ATAD5 nucleates a distinct RFC-like complex, defining a new genome-stability factor separate from the known Rad24- and Ctf18-RFC clamp loaders.

    Evidence Genetic interaction screens, reciprocal Co-IP, and epistasis in yeast across three independent labs

    PMID:12909721 PMID:12912927 PMID:13678589

    Open questions at the time
    • Biochemical activity of the complex on PCNA not yet defined
    • Mechanistic distinction from loading RFCs unresolved
  2. 2003 Medium

    Linked Elg1 physically to PCNA and the Okazaki fragment maturation machinery, providing the first clue that its substrate is the sliding clamp.

    Evidence Pulldown/two-hybrid and genetic interaction with Pol30 (PCNA) and Rad27/FEN-1 in yeast

    PMID:13678589

    Open questions at the time
    • Direction of PCNA regulation (load vs unload) not determined
    • Interaction not reconstituted with purified components
  3. 2010 High

    Defined ATAD5's scaffolding role by showing its N-terminus recruits the USP1-UAF1 deubiquitinase to remove monoubiquitin from PCNA, coupling clamp regulation to the ubiquitin pathway.

    Evidence Co-IP, siRNA knockdown, ubiquitin-PCNA western blot, and domain mapping in human cells; plus SUMO-PCNA/SIM-PIP recognition in yeast

    PMID:20147293 PMID:20571511

    Open questions at the time
    • Whether deubiquitination is mechanistically coupled to unloading not resolved
    • Roles of additional DUBs not yet explored
  4. 2011 High

    Demonstrated in vivo physiological relevance and disease link by showing Atad5 haploinsufficiency impairs PCNA deubiquitination and predisposes mice to tumors.

    Evidence Atad5+/m heterozygous mouse model, MEF deubiquitination assays, tumor incidence

    PMID:21901109

    Open questions at the time
    • Molecular link between PCNA deubiquitination defect and tumorigenesis indirect
    • Human disease mutation spectrum not addressed
  5. 2013 High

    Proved the core activity—that the complex directly unloads PCNA from chromatin—resolving the long-standing question of its enzymatic function.

    Evidence In vitro PCNA unloading with purified Elg1-RLC plus auxin degron in vivo (yeast); chromatin fractionation and ATPase mutants in human cells regulating replication factory lifespan

    PMID:23277426 PMID:23499004 PMID:23937667

    Open questions at the time
    • Trigger that times unloading not yet identified
    • Structural basis for unloading-only activity unknown
  6. 2015 High

    Identified the physiological signal for unloading by showing Okazaki fragment ligation is a prerequisite for genome-wide PCNA removal behind forks.

    Evidence ChIP-seq PCNA profiling, Cdc9 ligase degron, and heterologous Chlorella ligase complementation in yeast

    PMID:26212319

    Open questions at the time
    • How ligation status is sensed by the complex unclear
    • Lagging- vs leading-strand specificity not fully mapped
  7. 2016 High

    Established that the timing of PCNA clearance is critical, showing retention into G2/M—not S-phase retention alone—is the major driver of genome instability.

    Evidence Cell-cycle-regulated ELG1 alleles and disassembly-prone PCNA mutant rescue of genome instability in yeast

    PMID:27373149

    Open questions at the time
    • Downstream lesion caused by retained PCNA not pinpointed
    • Mammalian generalization of G2/M effect untested here
  8. 2019 High

    Expanded the functional reach of PCNA unloading to mismatch repair, fork restart, checkpoint signaling, and recombination, showing clamp residence time gates multiple genome-maintenance pathways.

    Evidence PCNA-mutant epistasis and MMR intermediate assays (yeast), ATAD5-RAD51 Co-IP and single-molecule FRET fork regression (human/mouse), Rad9/Dpb11 phosphorylation and ChIP (yeast), Rad51/Rad52 recruitment at collapsed forks (fission yeast)

    PMID:31114918 PMID:31149897 PMID:31186330 PMID:31844045

    Open questions at the time
    • Whether each pathway role is direct or a secondary consequence of PCNA retention varies by study
    • Cross-species mechanistic conservation not uniformly tested
  9. 2020 Medium

    Revealed a transcription-replication coordination role by showing ATAD5 recruits RNA helicases to forks and that PCNA unloading itself prevents R-loop accumulation, plus an RLC-independent centrosomal function.

    Evidence Co-IP and iPOND with DDX1/DDX5/DDX21/DHX9, S9.6 R-loop detection (human cells); immunofluorescence and centrosome counting with UAF1/ID1

    PMID:32542338 PMID:32594826

    Open questions at the time
    • Helicase recruitment mechanism not structurally defined
    • Whether centrosomal role uses deubiquitination scaffolding unclear
  10. 2023 High

    Defined ATAD5 as the dominant cellular unloader and a multi-DUB scaffold, and extended its substrate-clearance role to DSB end resection and DNA-methylation termination.

    Evidence Xenopus extract immunodepletion and ATPase mutants; in vitro DUB reconstitution with UAF1-USP1/USP7/USP11 and domain mapping; in vitro short-range resection system; PAF15 chromatin fractionation

    PMID:36734974 PMID:37739427 PMID:38141767 PMID:39145935

    Open questions at the time
    • Coordination between unloading and deubiquitination scaffolding not fully integrated
    • Substrate selectivity among PCNA-clamped processes incomplete
  11. 2024 High

    Provided the structural mechanism for why ATAD5-RFC unloads rather than loads PCNA, identifying locking loops and a plug domain and a unique protomer 2-3 gate.

    Evidence Cryo-EM structures from two independent labs with AMP-PNP and covalently closed circular DNA functional tests; BAZ1B Co-IP regulating deubiquitination timing

    PMID:38427736 PMID:38871854 PMID:39627214

    Open questions at the time
    • Structural state of the bound PCNA during ring opening not captured
    • How regulatory partners (BAZ1B) modulate the structural cycle unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ATAD5 integrates and prioritizes its multiple substrate-clearance functions (unloading, deubiquitination, helicase recruitment) at a single fork or lesion in real time remains unresolved.
  • No unified model coupling unloading kinetics to DUB scaffolding and helicase delivery
  • Spectrum and functional consequences of human ATAD5 disease alleles not defined in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140657 ATP-dependent activity 3 GO:0003677 DNA binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3 R-HSA-392499 Metabolism of proteins 2
Partners
BAZ1BPCNARAD51RFC2-5UAF1USP1USP11USP7
Complex memberships
ATAD5/Elg1-RFC-like complex (RLC)USP1-UAF1 deubiquitinase complex (heterotrimer with ATAD5)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ELG1/ATAD5 encodes the major subunit of a novel RFC-like complex (RLC) formed with RFC2-5 subunits, distinct from the Rad24-RFC and Ctf18-RFC complexes, and this complex is required for genome stability, S-phase progression, and Rad53 checkpoint kinase activation in response to replication stress. Genetic interaction screens, co-immunoprecipitation, biochemical fractionation, genetic epistasis with rad24 and ctf18 mutants The EMBO journal / Current biology / PNAS High 12909721 12912927 13678589
2003 Elg1 physically interacts with PCNA (Pol30) and the FEN-1 homolog Rad27, suggesting a role in Okazaki fragment maturation. Physical interaction assay (pulldown/two-hybrid), genetic interaction analysis Current biology : CB Medium 13678589
2004 Elg1 participates in negative control of telomere length and telomeric silencing through a replication-mediated pathway that is dependent on yKu, DNA polymerase, and active telomerase, but independent of recombination. Genetic epistasis with telomerase, yKu, and recombination mutants; telomere length assays Proceedings of the National Academy of Sciences of the United States of America Medium 14745004
2006 Elg1 is involved in homologous recombination (HR)-mediated DSB repair; it associates with both the DSB site (MAT locus) and the homologous donor locus (HML) in a Rad52-dependent manner at HML, and its loss reduces efficiency of primer extension after strand invasion and ligation steps of HR. Chromatin immunoprecipitation (ChIP), HR repair assays with HO endonuclease-induced DSBs, genetic epistasis Nucleic acids research Medium 17170004
2008 The unique C-terminus of Elg1 mediates oligomerization with Rfc2-5, nuclear import, and chromatin association; the Walker A motif in the conserved RFC region is dispensable for Elg1 function in vivo; the N-terminus contributes to genome stability and promotes nuclear localization. Mutational analysis, chromatin fractionation, nuclear localization assays DNA repair Medium 18482875
2009 Elg1-RLC plays a role in sister chromatid cohesion; elg1 mutants show elevated precocious sister chromatid separation and Elg1 is required for recruitment of Ctf18 to chromatin. Genetic interactions with cohesin subunits (Mcd1/Scc1) and cohesin loader (Scc2) were identified. Genetic suppressor screen, sister chromatid cohesion assays, chromatin localization by fractionation, genetic epistasis PloS one Medium 19262753 19430531
2010 Elg1 preferentially interacts with SUMOylated PCNA via three SUMO-interacting motifs (SIMs) and a PIP box near its N-terminus; in the absence of Elg1, SUMOylated PCNA and the helicase Srs2 accumulate on chromatin. Physical interaction assays, chromatin fractionation, SIM and PIP box mutagenesis, genetic epistasis with srs2 and PCNA modification mutants The EMBO journal High 20571511
2010 Human ELG1/ATAD5 interacts with the USP1-UAF1 deubiquitinating enzyme complex and directs it to deubiquitinate monoubiquitinated PCNA at stalled replication forks; the N-terminal domain of ELG1 is responsible for USP1-UAF1 interaction and PCNA deubiquitination activity. ELG1 knockdown specifically increases PCNA monoubiquitination without affecting FANCD2 ubiquitination. Co-immunoprecipitation, siRNA knockdown, western blot for ubiquitinated PCNA, N-terminal domain mapping The Journal of biological chemistry High 20147293
2011 Elg1 N-terminus physically interacts with SUMO-pathway proteins Slx5 and Slx8 (an E3 SUMO-targeted ubiquitin ligase complex), mediated by poly-SUMO chains requiring Siz2 activity, in a PCNA modification-independent manner. Yeast two-hybrid screen, physical interaction assays, genetic epistasis with SUMO pathway mutants Cell cycle (Georgetown, Tex.) Medium 21869594
2011 Atad5 haploinsufficiency in mice leads to defective PCNA deubiquitination in response to DNA damage in MEFs, demonstrating the in vivo tumor suppressor function of mammalian ATAD5 is linked to its PCNA deubiquitination activity. Mouse genetics (Atad5+/m heterozygous mice), MEF PCNA deubiquitination assays, tumor incidence monitoring PLoS genetics High 21901109
2012 ATAD5 regulates the lifespan of replication factories by unloading PCNA from chromatin during and after DNA synthesis; ATAD5 depletion extends replication factory lifespan, retains PCNA and replisome proteins on chromatin, decreases overall replication rate, and causes PCNA foci persistence into G2. The ATPase domain of ATAD5 is required for these activities. siRNA knockdown, PCNA chromatin fractionation, live imaging of replication factories, ATPase domain mutagenesis, flow cytometry The Journal of cell biology High 23277426
2013 The yeast Elg1-RLC directly unloads PCNA from chromatin during DNA replication in vivo and in vitro; without Elg1, PCNA accumulates on chromatin during replication and can be removed by switching Elg1 expression back on. Purified Elg1-RLC causes PCNA unloading in vitro and unloads both unmodified and SUMOylated PCNA. Improved auxin-inducible degron system, chromatin fractionation, in vitro PCNA unloading assay with purified Elg1-RLC Molecular cell High 23499004
2013 Human Elg1/ATAD5 depletion causes accumulation of chromatin-bound PCNA during S phase, increases PCNA foci, causes chromatin loop size increase, and leads to aberrant/lagging chromosomes in mitosis, confirming ATAD5 as a PCNA unloading factor in human cells. siRNA knockdown, chromatin fractionation, immunofluorescence imaging of PCNA foci, chromosome analysis Genes to cells : devoted to molecular & cellular mechanisms High 23937667
2015 The Elg1-RLC unloads PCNA genome-wide following Okazaki fragment ligation; in elg1Δ cells PCNA is retained on chromosomes in the wake of replication forks rather than at specific sites; Okazaki fragment ligation by Cdc9 is a prerequisite for PCNA unloading, as Chlorella virus ligase substituting for Cdc9 also promotes PCNA unloading. ChIP-seq genome-wide PCNA profiling, degron-mediated depletion of Cdc9 ligase, heterologous ligase complementation, chromatin fractionation Cell reports High 26212319
2015 Phosphorylation of Elg1 at S112 is dependent on the ATR ortholog Mec1 and is important for Elg1's role at telomeres and in regulation of DNA repair; Elg1 phosphorylation mutants unable to undergo phosphorylation suppress the DNA damage sensitivity of rad5Δ mutants. Mass spectrometry identification of phosphorylation sites, phosphorylation mutant analysis, epistasis with rad5Δ, telomere length assays Cell cycle (Georgetown, Tex.) Medium 26177013
2016 Prolonged retention of PCNA on DNA into G2/M phase is the major cause of genome instability in elg1Δ yeast; disassembly-prone PCNA mutants that relieve PCNA accumulation rescue genome instability of elg1Δ; PCNA retention specifically through G2/M exacerbates genome instability beyond that caused by S-phase retention alone. Cell-cycle-regulated ELG1 alleles engineering, disassembly-prone PCNA mutants, genome instability assays, overexpression-induced PCNA accumulation Cell reports High 27373149
2016 The Drosophila Enok KAT6 acetyltransferase complex physically interacts with the Elg1 PCNA-unloader complex and negatively regulates its PCNA-unloading function to promote G1/S transition; Enok depletion reduces chromatin-bound PCNA levels and causes a G1/S block that is partially rescued by Elg1 co-depletion. Co-immunoprecipitation, siRNA depletion, cell cycle analysis, chromatin-bound PCNA quantification in S2 cells and embryos Genes & development Medium 27198229
2017 Structure-function analysis of yeast Elg1 shows that the sensitivity to DNA damaging agents and hyper-recombination of ELG1 alleles correlate with their ability to unload PCNA; purified Elg1 complex inhibits DNA synthesis by unloading SUMOylated PCNA from DNA; ELG1 mutations suppress rad5Δ sensitivity by allowing trans-lesion synthesis. Homology modeling-guided site-specific mutagenesis, in vitro DNA synthesis inhibition assay with purified proteins, genetic epistasis Nucleic acids research High 28108661
2018 Elg1 interacts with the histone chaperone Rtt106 (identified by proteomics); the major cause of chromatin organization defects in elg1Δ is PCNA retention on DNA, with the Rtt106-Elg1 interaction playing a contributory role in post-replication nucleosome assembly. Proteomic interaction screen, Okazaki fragment length measurement, MNase sensitivity assay of newly replicated DNA, genetic epistasis PLoS genetics Medium 30418970
2019 Timely removal of PCNA from DNA by the Elg1 complex is important for efficient mismatch repair (MMR); over-retained PCNA in elg1Δ hyper-recruits Msh2-Msh6 through its PIP motif and causes accumulation of MMR intermediates. PCNA mutants that spontaneously fall off DNA attenuate the elg1Δ mutator phenotype, while PCNA mutants with enhanced DNA interactions exacerbate it. Epistasis analysis with PCNA mutants, mutation rate assays, Msh2-Msh6 chromatin recruitment assays Nucleic acids research High 31114918
2019 ATAD5 promotes replication restart at stalled forks by recruiting RAD51 in an ATR-dependent manner; ATAD5 also removes PCNA from stalled forks to enable RAD51 recruitment. PCNA itself acts as a mechanical barrier to fork regression as shown by single-molecule FRET; ATAD5 depletion inhibits fork regression and reduces DNA breaks required for fork restart. Co-immunoprecipitation of ATAD5-RAD51, chromatin fractionation, hydroxyurea treatment, single-molecule FRET with PCNA, native BrdU assay for fork regression, mouse HU treatment model Nature communications High 31844045
2019 Elg1 is essential for eliciting the DNA damage checkpoint (DC branch); in elg1 mutants, the adaptor proteins Rad9 (53BP1) and Dpb11 (TopBP1) are recruited to damage sites but fail to be phosphorylated by Mec1 (ATR), preventing checkpoint signal amplification. Local PCNA accumulation at damage sites in elg1 mutants correlates with checkpoint failure. Checkpoint-inducible strains, phosphorylation assays for Rad9/Dpb11, ChIP of PCNA at Lac operator sites, genetic epistasis mBio Medium 31186330
2019 The Elg1 PCNA unloader is necessary for efficient recruitment/retention of Rad51 and Rad52 at collapsed replication forks (RTS1 barrier) in fission yeast; PCNA unloading by Elg1 limits activity of anti-recombinogenic helicases Fbh1 and Srs2 to allow recombination to proceed. Replication fork collapse assays at RTS1 barrier, Rad51/Rad52 foci quantification, genetic epistasis with fbh1 and srs2 deletions eLife Medium 31149897
2020 ATAD5 interacts with RNA helicases DDX1, DDX5, DDX21, and DHX9, increasing their abundance at replication forks to facilitate R-loop resolution; additionally, ATAD5-mediated PCNA unloading prevents new R-loop generation behind replication forks by removing PCNA that would otherwise cause collision with transcription machinery. Co-immunoprecipitation, iPOND (isolation of proteins on nascent DNA), siRNA knockdown, R-loop detection (S9.6 antibody), replication rate assays Nucleic acids research High 32542338
2020 ATAD5 suppresses centrosome over-duplication; ATAD5 localizes to the base of mother and daughter centrioles. UAF1 (ATAD5 interactor) also localizes at the centrosome. ATAD5 depletion increases cells with over-duplicated centrosomes and multipolar chromosome segregation. The centrosomal function of ATAD5 does not require other RLC subunits. ATAD5 depletion reduces UAF1-ID1 interactions and increases ID1 centrosomal signal. Immunofluorescence co-localization, siRNA knockdown, centrosome counting, co-immunoprecipitation of UAF1-ID1, ATAD5 overexpression Cell cycle (Georgetown, Tex.) Medium 32594826
2020 Access to PCNA by Srs2 and Elg1 controls the choice between DDT pathways; SUMOylated PCNA recruits Srs2 to repress a 'salvage recombination' pathway; overexpression of Elg1 (the PCNA unloader) activates salvage recombination by removing SUMOylated PCNA and thereby limiting Srs2 recruitment. Genetic epistasis with PCNA modification mutants (pol30-K164R, pol30-KK127,164RR), recombination assays, Elg1 overexpression mBio Medium 32371600
2021 ATAD5-mediated PCNA unloading is important for timely termination of repair DNA synthesis at ROS-induced single-strand breaks (SSBs); ATAD5 depletion causes increased repair DNA synthesis and greater DNA polymerase stalling (measured by PCNA monoubiquitination) at H2O2-induced SSBs but not at MMS-induced base damage. PCNA is loaded at direct SSBs after 3'-end processing but rarely during BER of oxidized/alkylated bases. siRNA knockdown, H2O2 and MMS sensitivity assays, repair DNA synthesis measurement, PCNA monoubiquitination western blot, SSBR protein chromatin enrichment Nucleic acids research Medium 34718749
2022 The minimal PCNA-unloading domain (ULD) of ATAD5 was defined; the C-terminus of ULD is required for stable RFC2-5 association for active RLC formation; the N-terminus of ULD participates in opening the PCNA ring; ATAD5-RLC binds more robustly to open-labile PCNA than wild-type PCNA. Deletion/mutagenesis analysis of ATAD5 ULD, Co-IP of RFC2-5, PCNA unloading assays, binding assays with PCNA mutants Cells Medium 35681528
2023 ATAD5 is required for short-range end resection at DSBs; PCNA is rapidly loaded at DSB sites in an RFC and MRE11-RAD50-NBS1/CtIP-dependent manner, and ATAD5-mediated PCNA unloading is required for completion of short-range resection and removal of KU70/80 from DSB termini, facilitating DNA repair synthesis and HR completion. Cytological analysis of resection markers, in vitro short-range end resection system, siRNA knockdown, chromatin fractionation, HR repair assays, camptothecin sensitivity Nucleic acids research Medium 37739427
2023 Atad5-RLC is the major PCNA unloader in Xenopus egg extracts, providing the dominant PCNA unloading activity despite comprising only ~3% of RFC/RLCs; RFC and Ctf18-RLC immunodepletion do not detectably affect PCNA unloading rate. Atad5 PCNA unloading is dependent on ATP-binding, independent of DNA nicks and chromatin assembly, and inhibited by PCNA-interacting peptides. Xenopus egg extract PCNA unloading system, immunodepletion of Atad5/Rfc1/Ctf18, ATPase motif mutants, PCNA-interacting peptide inhibition assays The Journal of biological chemistry High 38141767
2023 ATAD5 (N-terminal domain) functions as a scaffold for Ub-PCNA deubiquitination by forming a heterotrimeric complex with UAF1-USP1; ATAD5 recognizes DNA-loaded Ub-PCNA through distinct DNA-binding and PCNA-binding motifs; ATAD5 also enhances Ub-PCNA deubiquitination by USP7 and USP11 through specific interactions, and promotes deubiquitination of poly-Ub-PCNA by all three USPs. Co-immunoprecipitation, in vitro deubiquitination assay, DNA-binding and PCNA-binding domain mapping, ATAD5 UAF1-binding mutants, sensitivity assays Proceedings of the National Academy of Sciences of the United States of America High 39145935
2023 ATAD5 removal of non-ubiquitinated PAF15 (PAF15Ub0) from chromatin is part of the termination mechanism for UHRF1-dependent maintenance DNA methylation; USP7 specifically deubiquitinates PAF15Ub2 in complex with DNMT1, and completion of DNA methylation by DNMT1 catalytic activity is required for termination of UHRF1-mediated ubiquitin signaling. Co-immunoprecipitation, siRNA depletion of ATAD5/USP7, chromatin fractionation, DNMT1 inhibition, interaction mapping eLife Medium 36734974
2023 SUMOylated PCNA acts as a positive signal for telomerase activity; Elg1 physically interacts with the CST complex (Cdc13-Stn1-Ten) and, together with Stn1, negatively regulates telomere elongation in a SUMO-coordinated manner. Telomere length assays, genetic epistasis with PCNA modification mutants, physical interaction assays between Elg1 and CST complex eLife Medium 37530521
2024 Cryo-EM structures of ATAD5-RFC/Elg1-RFC reveal two unique 'locking loops' that tie the complex into a rigid structure and a 'plug' domain filling the DNA-binding chamber, explaining why ATAD5-RFC exclusively unloads PCNA rather than loading it; ATAD5-RFC opens a PCNA gap between protomers 2 and 3 (distinct from gap between protomers 1 and 3 used by all known clamp loaders); ATAD5-RFC can unload PCNA using non-hydrolyzable AMP-PNP and can remove PCNA from covalently closed circular DNA, indicating unloading occurs by a mechanism distinct from loading. Cryo-EM structure determination, AMP-PNP non-hydrolyzable ATP analog experiments, PCNA unloading from covalently closed circular DNA Nature structural & molecular biology / Science advances High 38427736 38871854
2024 BAZ1B (regulatory subunit of the WICH chromatin-remodeling complex) binds ATAD5 at a region encompassing the UAF1-binding domain; disruption of ATAD5-BAZ1B interaction causes premature Ub-PCNA deubiquitination after H2O2 treatment, suggesting BAZ1B prevents premature Ub-PCNA deubiquitination to safeguard genome integrity. Co-immunoprecipitation of BAZ1B-ATAD5, ATAD5 mutants disrupting BAZ1B binding, Ub-PCNA deubiquitination assays, H2O2 sensitivity Nature communications Medium 39627214

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The Elg1 replication factor C-like complex functions in PCNA unloading during DNA replication. Molecular cell 220 23499004
2003 Elg1 forms an alternative RFC complex important for DNA replication and genome integrity. The EMBO journal 143 12912927
2003 Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability. Current biology : CB 134 13678589
2010 Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear antigen (PCNA) through Its interactions with PCNA and USP1. The Journal of biological chemistry 122 20147293
2003 ELG1, a yeast gene required for genome stability, forms a complex related to replication factor C. Proceedings of the National Academy of Sciences of the United States of America 115 12909721
2012 ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin. The Journal of cell biology 113 23277426
2010 Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA. The EMBO journal 91 20571511
2015 Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and Requires Okazaki Fragment Ligation. Cell reports 89 26212319
2011 Predisposition to cancer caused by genetic and functional defects of mammalian Atad5. PLoS genetics 75 21901109
2004 ELG1, a regulator of genome stability, has a role in telomere length regulation and in silencing. Proceedings of the National Academy of Sciences of the United States of America 68 14745004
2020 ATAD5 restricts R-loop formation through PCNA unloading and RNA helicase maintenance at the replication fork. Nucleic acids research 61 32542338
2016 PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1. Cell reports 59 27373149
2009 The ELG1 clamp loader plays a role in sister chromatid cohesion. PloS one 58 19430531
2009 The Elg1-RFC clamp-loading complex performs a role in sister chromatid cohesion. PloS one 57 19262753
2009 DNA damage responses by human ELG1 in S phase are important to maintain genomic integrity. Cell cycle (Georgetown, Tex.) 53 19755857
2019 ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress. Nature communications 46 31844045
2004 Increased genome instability and telomere length in the elg1-deficient Saccharomyces cerevisiae mutant are regulated by S-phase checkpoints. Eukaryotic cell 44 15590829
2013 Is PCNA unloading the central function of the Elg1/ATAD5 replication factor C-like complex? Cell cycle (Georgetown, Tex.) 41 23907118
2005 The Elg1 replication factor C-like complex: a novel guardian of genome stability. DNA repair 39 15725622
2017 A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance. Nucleic acids research 37 28108661
2013 Alternative replication factor C protein, Elg1, maintains chromosome stability by regulating PCNA levels on chromatin. Genes to cells : devoted to molecular & cellular mechanisms 31 23937667
2006 Role of Elg1 protein in double strand break repair. Nucleic acids research 30 17170004
2021 Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair. Nucleic acids research 25 34718749
2011 Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins. Cell cycle (Georgetown, Tex.) 25 21869594
2005 Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation in the absence of fully functional RFC in fission yeast. Nucleic acids research 23 16040599
2016 Rare ATAD5 missense variants in breast and ovarian cancer patients. Cancer letters 22 27045477
2019 Effective mismatch repair depends on timely control of PCNA retention on DNA by the Elg1 complex. Nucleic acids research 21 31114918
2020 ATAD5 deficiency alters DNA damage metabolism and sensitizes cells to PARP inhibition. Nucleic acids research 19 32297953
2008 The N- and C-termini of Elg1 contribute to the maintenance of genome stability. DNA repair 18 18482875
2020 Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in Saccharomyces cerevisiae. mBio 17 32371600
2018 Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation. PLoS genetics 15 30418970
2016 The Enok acetyltransferase complex interacts with Elg1 and negatively regulates PCNA unloading to promote the G1/S transition. Genes & development 15 27198229
2014 Elg1, a central player in genome stability. Mutation research. Reviews in mutation research 14 25795125
2013 Genetic and physical interactions between the yeast ELG1 gene and orthologs of the Fanconi anemia pathway. Cell cycle (Georgetown, Tex.) 14 23624835
2023 The termination of UHRF1-dependent PAF15 ubiquitin signaling is regulated by USP7 and ATAD5. eLife 13 36734974
2016 Hepatitis B Virus X Protein Upregulates hELG1/ ATAD5 Expression through E2F1 in Hepatocellular Carcinoma. International journal of biological sciences 13 26722215
2015 Regulation of Elg1 activity by phosphorylation. Cell cycle (Georgetown, Tex.) 13 26177013
2019 The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint. mBio 12 31186330
2014 ATAD5 deficiency decreases B cell division and Igh recombination. Journal of immunology (Baltimore, Md. : 1950) 12 25404367
2020 ATAD5 suppresses centrosome over-duplication by regulating UAF1 and ID1. Cell cycle (Georgetown, Tex.) 10 32594826
2024 The human ATAD5 has evolved unique structural elements to function exclusively as a PCNA unloader. Nature structural & molecular biology 9 38871854
2024 ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair. Nature communications 7 39627214
2022 Distinct Motifs in ATAD5 C-Terminal Domain Modulate PCNA Unloading Process. Cells 7 35681528
2019 A role for the yeast PCNA unloader Elg1 in eliciting the DNA damage checkpoint. Current genetics 7 31332476
2024 Structure of the PCNA unloader Elg1-RFC. Science advances 6 38427736
2024 ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination. Proceedings of the National Academy of Sciences of the United States of America 6 39145935
2019 The PCNA unloader Elg1 promotes recombination at collapsed replication forks in fission yeast. eLife 6 31149897
2023 Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination. Nucleic acids research 4 37739427
2023 The Atad5 RFC-like complex is the major unloader of proliferating cell nuclear antigen in Xenopus egg extracts. The Journal of biological chemistry 4 38141767
2023 Effects of Defective Unloading and Recycling of PCNA Revealed by the Analysis of ELG1 Mutants. International journal of molecular sciences 3 36675081
2023 Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader. eLife 3 37530521
2025 A replication stress safeguard provided by the Elg1 Replication Factor C-like complex. Genetics 0 40985265
2025 Novel mechanism of tumor metastasis: DDX11-ATAD5 interaction mediates epithelial-mesenchymal transition to promote gallbladder cancer progression. CytoJournal 0 41664698
2017 A New Method, "Reverse Yeast Two-Hybrid Array" (RYTHA), Identifies Mutants that Dissociate the Physical Interaction Between Elg1 and Slx5. Genetics 0 28476868

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