| 1999 |
The Mre11/Rad50/Nbs1 triple complex binds DNA cooperatively and displays enzymatic activities not seen without Nbs1, including partial duplex unwinding and efficient hairpin cleavage; ATP controls a switch in endonuclease specificity allowing cleavage of 3'-protruding strands at double/single-strand transitions; mutational analysis showed Rad50 is responsible for ATP binding but ATP-dependent activities require Nbs1. |
In vitro biochemical reconstitution with recombinant proteins; mutational analysis of Rad50 ATP-binding; endonuclease and unwinding assays |
Genes & development |
High |
10346816
|
| 2000 |
RAD50, MRE11, and NBS1 associate with TRF2 at human telomeres as demonstrated by nanoelectrospray tandem mass spectrometry and co-immunoprecipitation; NBS1 associates with TRF2 and telomeres specifically in S phase but not G1 or G2; MRE11 and RAD50 are present at interphase telomeres by indirect immunofluorescence. |
Nanoelectrospray tandem mass spectrometry; co-immunoprecipitation; indirect immunofluorescence; cell-cycle synchronization |
Nature genetics |
High |
10888888
|
| 2001 |
In S. cerevisiae, Tel1 (ATM homolog) and the Mre11 complex define a DNA damage checkpoint pathway that triggers Rad53 activation and its interaction with Rad9 in mitosis, and acts via Rad9/Mek1 in meiosis; the Mre11 complex functions as a damage sensor upstream of Tel1 in this pathway, and the pathway is required for unprocessed DSBs in meiosis. |
Genetic epistasis analysis; checkpoint kinase activation assays; yeast genetics |
Molecular cell |
High |
11430828
|
| 2001 |
Xenopus Mre11 complex is required to prevent accumulation of DNA double-strand breaks during chromosomal DNA replication; immunodepletion of X-Mre11 complex from cell-free extracts leads to accumulation of DSBs (detected by TUNEL and γ-H2AX) in replicated DNA; DSBs stimulate phosphorylation and 3′-5′ exonuclease activity of X-Mre11 complex in an ATM-independent manner. |
Xenopus egg cell-free extract system; immunodepletion; TUNEL assay; γ-H2AX immunoblotting; exonuclease activity assay |
Molecular cell |
High |
11511367
|
| 2004 |
Mre11 assembles linear DNA fragments into a high-molecular-weight DNA damage signaling complex that includes MRN, damaged DNA molecules, and activated ATM in Xenopus egg extracts; complex formation requires an intact Mre11 C-terminal domain deleted in some ATLD patients; the ATLD truncation can still perform replication functions of Mre11. |
Xenopus egg extract biochemistry; gel filtration/sedimentation; immunoprecipitation; functional complementation with truncation mutants |
PLoS biology |
High |
15138496
|
| 2004 |
Nuclear expression of Mre11-Rad50 (but not Nbs1 alone) stimulates ATM activation at early times after low radiation doses; Mre11-Rad50 also acts as an adaptor for ATM-dependent phosphorylation of nibrin and Chk2 but not Smc1; Nbs1's essential nuclear localization role can be uncoupled from its role in ATM activation. |
Isogenic cell lines expressing nuclear vs. cytoplasmic MRN components; ATM kinase activation assays; phospho-substrate immunoblotting after irradiation |
The Journal of biological chemistry |
High |
15234984
|
| 2004 |
The nuclease-deficient mre11-3 (H85L) mutant retains wild-type DNA binding and Rad50/Nbs1 interaction but completely abolishes nuclease activity; crystal structure at 2.3 Å reveals an active-site geometry with wild-type metal-binding environment but inability to hydrolyze DNA, demonstrating structural separation of DNA binding and catalysis. |
Crystal structure determination (2.3 Å); in vitro nuclease assays; co-immunoprecipitation; DNA binding assays; IRIF formation assays |
Nucleic acids research |
High |
15047855
|
| 2004 |
Werner syndrome protein (WRN) associates with the Mre11 complex via direct binding to Nbs1 in vitro and in vivo; Nbs1 is required for Mre11 complex promotion of WRN helicase activity; WRN co-localizes with the Mre11 complex in response to γ-irradiation or mitomycin C. |
Co-immunoprecipitation in vitro and in vivo; siRNA/complementation; co-localization immunofluorescence; helicase activity assay |
The Journal of biological chemistry |
High |
15026416
|
| 2005 |
Purified recombinant MRE11/RAD50 cleaves DNA at abasic (AP) sites via an AP-lyase activity conserved from humans to Archaea; cleavage occurs within single-stranded regions of DNA; MRE11 associates specifically with rearranged Ig genes in hypermutating B cells whereas APE1 does not, implicating MRN in the AID/UNG-dependent immunoglobulin gene diversification pathway. |
Purified recombinant protein in vitro AP-lyase assay; chromatin immunoprecipitation (ChIP) in hypermutating B cells |
Molecular cell |
High |
16285919
|
| 2007 |
Mre11/Rad50 complexes from three organisms catalyze the reversible adenylate kinase reaction in vitro; mutation of the conserved Rad50 signature motif reduces adenylate kinase activity without reducing ATPase; an adenylate kinase inhibitor blocks MR-dependent DNA tethering in vitro and in cell-free extracts; this activity correlates with meiosis and telomere maintenance functions in S. cerevisiae. |
In vitro adenylate kinase assays with purified proteins from three organisms; Rad50 mutagenesis; DNA tethering assays; S. cerevisiae genetics |
Molecular cell |
High |
17349953
|
| 2008 |
Crystal structure and SAXS analysis of Pyrococcus furiosus Mre11 dimers bound to DNA reveal a four-lobed U-shaped dimer structure critical for MRN complex assembly and DNA end alignment; mutations blocking Mre11 endonuclease activity impair cell survival after DSB induction without affecting MRN complex assembly or Mre11-dependent Ctp1 recruitment. |
Crystal structure; SAXS; mutagenesis of fission yeast Mre11; cell survival assays; co-immunoprecipitation |
Cell |
High |
18854158
|
| 2010 |
Mre11-Rad50-Xrs2 (MRX) and Sae2 stimulate 5′-strand resection in a biochemically reconstituted system; degradation of the 5′ strand is catalyzed by Exo1 but is completely dependent on MRX and Sae2 when Exo1 is limiting; stimulation is mainly due to cooperative DNA binding by Exo1, MRX, and Sae2. |
Biochemical reconstitution with purified MRX, Sae2, and Exo1; in vitro resection assays; DNA binding assays |
Nature structural & molecular biology |
High |
21102445
|
| 2010 |
The Mre11-Rad50-Xrs2 (MRX) complex stimulates DNA end resection by the Dna2-Sgs1-RPA machinery by promoting complex formation with Sgs1, which unexpectedly stimulates Sgs1 DNA unwinding activity. |
Biochemical reconstitution with purified proteins; in vitro DNA resection and unwinding assays |
Nature |
High |
20811461
|
| 2010 |
ATM suppresses DNA end-degradation and microhomology-mediated end joining (MMEJ) in a kinase-activity-dependent manner; Mre11 is the major nuclease responsible for DNA end-degradation and MMEJ in ATM-deficient cells; Mre11 nuclease inhibition (mirin) or knockdown reduces MMEJ repair. |
MMEJ reporter assay; Mre11 knockdown; mirin inhibitor; ATM kinase assays; structure-based modeling |
Cell cycle |
Medium |
20647759
|
| 2011 |
Mre11 endonuclease nicks the 5′-strand up to 300 nucleotides from the DSB end, enabling bidirectional resection: Exo1 resects 5′→3′ away from the DSB and Mre11 exonuclease resects 3′→5′ toward the DSB end; both exonuclease activities of Mre11 and Exo1 are required for efficient DSB repair in S. cerevisiae. |
In vivo physical assays for 5′-end processing in S. cerevisiae meiosis; exo1 and mre11 nuclease mutant analysis; Southern blotting |
Nature |
High |
22002605
|
| 2011 |
MRE11 arginine methylation by PRMT1 within its glycine-arginine-rich (GAR) motif is required for DSB end resection and ATR/CHK1 checkpoint signaling; Mre11(RK) knock-in cells (arginines replaced with lysines) show exonuclease and DNA-binding defects in vitro, impaired RPA and RAD51 recruitment, and ATR/CHK1 signaling defects; ATM pathway activation by the M(RK)RN complex is unaffected. |
Mouse knock-in allele; in vitro exonuclease and DNA-binding assays; immunofluorescence; immunoblotting for checkpoint kinases; γ-irradiation sensitivity |
Cell research |
High |
21826105
|
| 2011 |
Xrs2/Nbs1 is essential for nuclear translocation of Mre11; nuclear localization of Mre11 (Mre11-NLS) bypasses Xrs2 for DNA end resection, meiosis, hairpin resolution, and clastogen resistance; purified MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends; Xrs2 is required for Tel1/ATM kinase signaling and NHEJ, acting as a chaperone/adaptor. |
Genetic bypass experiments; in vitro reconstitution with purified MR and MRX; yeast genetic assays; Tel1 signaling assays |
Molecular cell |
High |
27746018
|
| 2013 |
Structure-based design identified specific MRE11 endo- or exonuclease inhibitors; endonuclease inhibition promotes NHEJ over HR at G2 DSBs while exonuclease inhibition confers a repair defect; MRE11 endonuclease initiates resection to license HR, followed by MRE11 exonuclease and EXO1/BLM bidirectional resection; both nuclease activities regulate repair pathway choice. |
Structure-based chemical library design; specific nuclease inhibitors; RPA chromatin binding; NHEJ vs. HR repair outcome assays in irradiated G2 cells |
Molecular cell |
High |
24316220
|
| 2013 |
MRN-dependent DNA end resection and HR repair can occur independently of H2AX-mediated signaling; the MRN complex promotes DNA end resection and generation of ssDNA critical for HR, and these functions are separable from H2AX-dependent recruitment of 53BP1 and BRCA1. |
H2AX-deficient cell lines; HR reporter assays; RPA/ssDNA generation assays; epistasis |
The Journal of biological chemistry |
Medium |
19910469
|
| 2013 |
Single-molecule FRET reveals that MRN unwinds 15–20 base pairs at the end of a duplex in an ATP-dependent manner; a Rad50 catalytic domain mutant deficient in this ATP-dependent opening is impaired in DNA end resection in vitro and in resection-dependent repair in human cells. |
Single-molecule FRET; Rad50 mutagenesis; in vitro resection assay; human cell repair assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
24191051
|
| 2015 |
Cryo-EM/crystal structure of Methanococcus jannaschii Mre11/Rad50 with ATPγS and DNA reveals that duplex DNA runs symmetrically across the central groove between two ATPγS-bound Rad50 domains; duplex DNA cannot access the Mre11 active site in the ATP-free full-length MR complex; ATP hydrolysis drives rotation of the nucleotide-binding domain and induces DNA melting to allow substrate access to Mre11. |
Crystal structure with ATPγS and DNA; in vitro ATPase and nuclease assays; structural comparison of ATP-free vs. ATP-bound states |
The EMBO journal |
High |
26717941
|
| 2015 |
Mre11-Sae2 and RPA prevent palindromic gene amplification by processing hairpin-capped DNA ends; loss of Sae2 or the Mre11 nuclease combined with RPA dysfunction increases palindromic duplications ~1,000-fold, indicating that RPA prevents intra-strand annealing and Mre11-Sae2 processes hairpin-capped chromosomes to prevent palindromic duplication. |
S. cerevisiae genetics; physical assays for palindromic duplication frequency; epistasis; Mre11 nuclease mutants |
Molecular cell |
High |
26545079
|
| 2016 |
Cyclin A2 controls Mre11 protein abundance through a C-terminal RNA-binding domain that directly binds Mre11 mRNAs to mediate polysome loading and translation; loss of cyclin A2's ability to upregulate Mre11 in S phase leads to impaired resolution of stalled replication forks and DSB repair. |
RNA binding assays; polysome profiling; Mre11 protein quantification in cyclin A2 mutant mice; replication fork analysis; DSB repair assays |
Science |
High |
27708105
|
| 2017 |
GRB2 forms a biophysically validated complex with MRE11; the GRB2-SH2 domain targets the GRB2-MRE11 complex to phosphorylated H2AX at DSBs; GRB2 K109 ubiquitination by RBBP6 releases MRE11 to promote HDR; loss of GRB2 increases MRE11-XRCC1 complex formation and alternative end joining (Alt-EJ). |
Co-immunoprecipitation; biophysical binding assays; ubiquitination assay; HR/Alt-EJ reporter assays; RBBP6 depletion; GRB2 knockout |
Science advances |
High |
34348893
|
| 2017 |
Polo-like kinase 1 (Plk1) phosphorylates Mre11 at serine 649, which primes subsequent CK2-mediated phosphorylation at serine 688; phosphorylation at S649/S688 inhibits loading of the MRN complex to damaged DNA, leading to premature DNA damage checkpoint termination and inhibition of DNA repair. |
In vitro kinase assays; phospho-specific antibodies; chromatin loading assays; DNA repair and checkpoint assays; Plk1 and CK2 inhibitors |
Cancer research |
Medium |
28512243
|
| 2017 |
The Mre11-Nbs1 interaction is essential for viability; a 108-amino-acid Nbs1 fragment comprising the Mre11 interface is sufficient to rescue viability and ATM activation in cultured cells and support hematopoietic differentiation in vivo; most of the Nbs1 protein is dispensable for essential Mre11 complex functions. |
TALEN-based genome editing to derive Nbs1mid mice; cell viability and ATM activation assays; in vivo hematopoietic differentiation |
Cell reports |
High |
28076792
|
| 2017 |
Single-molecule microscopy shows MRN searches for DNA ends by one-dimensional facilitated diffusion on nucleosome-coated DNA; Rad50 binds homoduplex DNA and promotes diffusion, while Mre11 is required for DNA end recognition and nuclease activities; MRN removes Ku or DNA adducts from occluded ends via an Mre11-dependent nucleolytic reaction; MRN loads Exo1 onto free DNA ends and acts as a processivity factor for Exo1 during long-range resection with RPA. |
High-throughput single-molecule microscopy; nucleosome-coated DNA substrates; Mre11 and Rad50 domain-specific mutants; resection assays with RPA and Exo1 |
Molecular cell |
High |
28867292
|
| 2017 |
MRE11 stability is regulated by CK2-dependent phosphorylation at serines 558/561 and 688/689 of MRE11, which enables binding to the PIH1D1 subunit of the R2TP cochaperone complex; depletion of PIH1D1 causes MRE11 destabilization and impairs MRE11-dependent DNA repair. |
Co-immunoprecipitation; CK2 phosphorylation mapping; phospho-mutant stability assays; PIH1D1 depletion; DNA repair assays |
Oncogene |
Medium |
28436950
|
| 2018 |
DYNLL1 directly binds MRE11 in vitro and limits MRE11-dependent DNA end resection in BRCA1-mutant cells; loss of DYNLL1 restores homologous recombination in BRCA1-mutant cells and confers platinum/PARPi resistance. |
CRISPR loss-of-function screen; direct in vitro binding assay (DYNLL1–MRE11); end resection assays; HR reporter; drug sensitivity assays |
Nature |
High |
30464262
|
| 2018 |
GFI1 interacts with PRMT1 and its substrates MRE11 and 53BP1; GFI1 enables PRMT1 to bind and methylate MRE11, which is necessary for MRE11 function in the DNA damage response. |
Co-immunoprecipitation; in vitro methylation assays; GFI1 deletion/complementation; DNA damage response assays |
Nature communications |
Medium |
29651020
|
| 2019 |
MRE11 is UFMylated at K282 by a UFM1 E3 ligase; UFMylation is required for MRN complex formation under unperturbed conditions and for DSB-induced optimal ATM activation and HR-mediated repair; a pathogenic cancer mutation MRE11(G285C) phenocopies the UFMylation-defective K282R mutant. |
UFMylation site mapping; K282R and G285C mutant expression; Co-IP for MRN complex formation; ATM activation assays; HR reporter assay |
Nucleic acids research |
Medium |
30783677
|
| 2019 |
Cryo-EM structures of E. coli Mre11-Rad50 homolog SbcCD in resting and DNA-bound cutting states reveal: in the resting state, Mre11 nuclease is blocked by ATP-bound Rad50; upon DNA binding, the two Rad50 coiled coils zip into a rod and together with nucleotide-binding domains clamp around dsDNA; Mre11 moves to the side of Rad50, binds the DNA end, and assembles a DNA cutting channel for nuclease reactions. |
Cryo-EM structure determination; biochemical DNA cleavage assays; domain mutagenesis |
Molecular cell |
High |
31492634
|
| 2019 |
MRN complex suppresses R-loops and associated DNA damage at transcription-replication conflicts through a non-nucleolytic function of MRE11 that is important for R-loop suppression by the Fanconi Anemia pathway. |
Genome-wide trigenic interaction screen in yeast; R-loop detection; genetic epistasis with FA pathway mutants; nuclease-dead Mre11 mutants |
Nature communications |
Medium |
31537797
|
| 2021 |
MRE11A deficiency disrupts mitochondrial oxygen consumption and ATP generation in T cells; MRE11A loss causes leakage of mitochondrial DNA (mtDNA) into the cytosol, triggering inflammasome assembly, caspase-1 activation, and pyroptotic cell death; MRE11A overexpression restores mitochondrial fitness and prevents tissue inflammation. |
MRE11A knockdown/overexpression; mitochondrial respiration assays; mtDNA cytosolic leakage detection; inflammasome/caspase-1 activation assays; in vivo mouse model |
Cell metabolism |
High |
31327667
|
| 2022 |
Cryo-EM structure of the eukaryotic Mre11-Rad50-Nbs1 (MRN) complex reveals a 2:2:1 stoichiometry with a single Nbs1 wrapping around the autoinhibited Mre11 nuclease dimer; MRN has two DNA-binding modes (ATP-dependent for loading onto DNA ends and ATP-independent via Mre11 C-terminus); two 60-nm coiled-coil domains form a linear rod joined at zinc-hook apices; two MRN complexes can dimerize via apices to form 120-nm structures. |
Cryo-EM structure determination; biochemical DNA binding assays; structural analysis of coiled-coil domain organization |
Molecular cell |
High |
36577401
|
| 2022 |
Cryo-EM structures of SbcCD (bacterial Mre11-Rad50 homolog) bound to a protein-blocked DNA end and a DNA hairpin reveal that Mre11-Rad50 bends internal DNA for endonucleolytic cleavage; the complex is loaded onto blocked DNA ends with Mre11 pointing away from the block, explaining the distinct biochemistries of 3′→5′ exonucleolytic vs. endonucleolytic incision. |
Cryo-EM structure determination of two substrate-bound states; biochemical nuclease assays |
Molecular cell |
High |
35987200
|
| 2022 |
RNF126 E3 ubiquitin ligase ubiquitinates MRE11 at K339 and K480, increasing its DNA exonuclease activity, subsequent RPA binding, and ATR phosphorylation; RNF126 depletion leads to genomic instability and radiation sensitivity; RNF126 expression is induced by IR via HER2-AKT-NF-κB signaling. |
Co-immunoprecipitation; ubiquitination mapping; in vitro exonuclease activity assays; RPA binding; ATR/CHK1 activation assays; RNF126 depletion in cells and mice |
Advanced science |
Medium |
36563124
|
| 2022 |
PIAS1 promotes MRE11 SUMOylation on chromatin to initiate DNA end resection; SENP3 deSUMOylates MRE11 mainly after it moves away from DSB sites; SENP3 deficiency causes MRE11 accumulation on chromatin and genome instability; SUMOylation protects MRE11 from ubiquitin-mediated degradation at DSB sites. |
SUMOylation mapping; PIAS1/SENP3 knockdown; ChIP; ubiquitination assays; DNA end resection assays; cancer mutant analysis |
Nature communications |
Medium |
36050397
|
| 2022 |
S. cerevisiae Mre11-Rad50 (with or without Xrs2) forms higher-order oligomeric assemblies in solution and on DNA; Rad50 mediates oligomerization; mutations in a conserved Rad50 β-sheet alter oligomerization; MRX oligomerization facilitates foci formation, DNA damage signaling, and repair in vivo; oligomerization drives endonucleolytic cleavage at multiple 5′-strand sites near DSBs without affecting exonuclease activity. |
Electron microscopy; biochemical oligomerization assays; Rad50 β-sheet mutagenesis; in vivo foci formation; DNA damage signaling and repair assays; in vitro endonuclease assays |
Nature communications |
High |
35501303
|
| 2022 |
METTL16 interacts with MRE11 through RNA and inhibits MRE11's exonuclease activity in a methyltransferase-independent manner, repressing DNA end resection; upon DNA damage, ATM phosphorylates METTL16 causing conformational change and autoinhibition of its RNA binding, which dissociates the METTL16-RNA-MRE11 complex and releases MRE11. |
Co-immunoprecipitation; in vitro exonuclease assays; ATM phosphorylation assays; METTL16 conformational analysis; HR assays |
Nature cancer |
Medium |
36138131
|
| 2022 |
PARP14 is a critical co-factor for MRE11 at stalled replication forks in BRCA-deficient cells; PARP14 catalytic activity mediates MRE11 engagement at nascent DNA; KU complex binds reversed forks and protects against EXO1-mediated degradation; KU recruits the PARP14-MRE11 complex, which initiates partial resection to release KU and allow long-range EXO1 resection. |
iPOND; chromatin fractionation; PARP14 depletion/inhibition; fork degradation assays (DNA fiber); KU depletion; sequential resection analysis |
Nature communications |
High |
36030235
|
| 2022 |
POLθ processes stalled Okazaki fragments to suppress ssDNA gaps on lagging strands in the absence of RAD51; inhibition of POLθ allows these fork gaps to be cleaved by the MRE11-NBS1-CtIP endonuclease, producing broken forks with asymmetric single-ended DSBs that impair BRCA2-defective cell survival. |
Xenopus laevis biochemistry; electron microscopy visualization of Okazaki fragments; POLθ inhibition; MRE11-NBS1-CtIP depletion; fork structure analysis |
Molecular cell |
High |
36400008
|
| 2023 |
MRE11 is lactylated at K673 by the CBP acetyltransferase in response to DNA damage; lactylation is dependent on ATM phosphorylation of CBP; MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and homologous recombination; inhibition of CBP or LDH reduces MRE11 lactylation, impairing HR. |
Site-specific lactylation mapping; CBP acetyltransferase assays; ATM phosphorylation assays; DNA binding assays; HR reporter; cell-penetrating peptide blocking; patient-derived xenograft and organoid models |
Cell |
High |
38128537
|
| 2023 |
DYNLL1 is recruited to DSBs by 53BP1 where it limits end resection by binding and disrupting the MRE11 dimer; the Shieldin complex is recruited to DSBs hours after DYNLL1 and its localization depends on MRE11 activity and is regulated by DYNLL1-MRE11 interaction; constitutive DYNLL1-MRE11 association resensitizes Shieldin-loss BRCA1-deficient cells to PARPi. |
Co-immunoprecipitation; MRE11 dimer disruption assay; DSB recruitment kinetics; Shieldin localization; PARPi sensitivity assays |
Nature structural & molecular biology |
High |
37696958
|
| 2023 |
ssDNA gaps at stalled replication forks are extended bidirectionally by MRE11 in the 3′→5′ direction and by EXO1 in the 5′→3′ direction; subsequently the parental strand at the ssDNA gap is cleaved by the MRE11 endonuclease to generate a DSB; this process is suppressed by the BRCA pathway. |
DNA fiber assays; MRE11 and EXO1 inhibition/depletion; ssDNA gap and DSB detection; BRCA pathway genetic interaction analysis |
Nature communications |
Medium |
37805499
|
| 2024 |
The MRE11-RAD50-NBN complex binding to nucleosome fragments is necessary to displace cGAS from acidic-patch-mediated sequestration, enabling cGAS mobilization and activation by dsDNA; MRE11 is therefore essential for cGAS activation in response to oncogenic stress, cytosolic dsDNA, and ionizing radiation; MRE11-dependent cGAS activation promotes ZBP1-RIPK3-MLKL-mediated necroptosis to suppress breast tumorigenesis. |
Nucleosome binding assays; cGAS displacement assays; MRE11 depletion/knockout; cGAS activation readouts; necroptosis assays; mouse mammary tumor models |
Nature |
High |
38200309
|
| 2024 |
UFL1 UFMylates PTIP at K148 upon replication stress; this facilitates PTIP-MLL3/4 complex assembly, H3K4me1/me3 enrichment at stalled forks, and subsequent MRE11 nuclease recruitment to degrade nascent DNA strands; loss of UFL1 or disruption of PTIP UFMylation protects stalled forks from MRE11-mediated degradation and confers PARPi resistance in BRCA1/2-deficient cells. |
UFMylation mapping; Co-immunoprecipitation; ChIP for histone marks; DNA fiber assays; MRE11 recruitment assays; UFSP2 overexpression; PARPi sensitivity assays |
Nature chemical biology |
Medium |
38649452
|
| 2003 |
The Mre11 complex is deposited on chromatin in an S phase-specific manner that is resistant to detergent extraction; it co-localizes extensively with PCNA throughout S phase; chromatin loading is enhanced by replication fork stalling; the complex localizes to ssDNA in hydroxyurea-treated cells; neither DNA damage nor γ-H2AX is required for Mre11 complex chromatin loading in S phase. |
Cell synchronization; chromatin fractionation with detergent extraction; co-immunofluorescence with PCNA; hydroxyurea treatment; γ-H2AX immunostaining |
Molecular cancer research : MCR |
Medium |
12556560
|
| 2004 |
RPA and the MRN complex co-localize to discrete foci and physically interact (co-immunoprecipitate) in response to HU- or UV-induced replication fork blockage; both RPA and Mre11 are phosphorylated and accumulate in chromatin-bound fractions upon replication stress; phosphatase treatment abrogates the RPA-MRN co-immunoprecipitation, suggesting phosphorylation mediates the interaction. |
Co-immunoprecipitation; chromatin fractionation; immunofluorescence; phosphatase treatment; HU/UV treatment |
The Journal of biological chemistry |
Medium |
15180989
|