Affinage

TP53BP1

TP53-binding protein 1 · UniProt Q12888

Length
1972 aa
Mass
213.6 kDa
Annotated
2026-04-28
100 papers in source corpus 51 papers cited in narrative 51 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

53BP1 is a central chromatin-based scaffold that directs DNA double-strand break repair pathway choice by promoting non-homologous end joining (NHEJ) and suppressing homologous recombination, while also amplifying p53 signaling and safeguarding genome integrity during replication and mitosis. Recruitment to DSBs requires bivalent nucleosome recognition — the tandem Tudor domain binds H4K20me2 while the UDR motif engages RNF168-catalyzed H2AK15ub, as revealed by cryo-EM — and this recognition is gated by regulators including TIRR (which masks the Tudor domain), SPOP-mediated ubiquitination (which extracts 53BP1 from chromatin in S phase), CBP/HDAC2-controlled UDR acetylation, and cell-cycle-dependent H4K20me2 dilution during replication (PMID:27462807, PMID:28241136, PMID:34144977, PMID:29190394, PMID:28564601). ATM-dependent phosphorylation of 53BP1 recruits distinct effectors — RIF1 via LxL-phosphopeptide motifs and PTIP via separate phospho-sites — with RIF1 in turn recruiting the shieldin complex (SHLD1–SHLD2–SHLD3–REV7) and CST–Polα to protect DNA ends from resection and execute fill-in synthesis, collectively enabling class-switch recombination and long-range V(D)J joining (PMID:23727112, PMID:35216668, PMID:30022168, PMID:30022158, PMID:18931658). Beyond DSB repair, 53BP1 undergoes liquid–liquid phase separation that concentrates p53 and amplifies its transcriptional output, forms nuclear bodies that restrain replication timing of under-replicated loci, and functions with USP28 and TP53 in a mitotic surveillance pathway that eliminates cells after prolonged mitosis (PMID:31267591, PMID:30804506, PMID:33226141).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Establishing that 53BP1 is an ATM substrate that forms DNA-damage-induced nuclear foci answered the foundational question of how 53BP1 is activated in the damage response, placing it within the ATM signaling axis.

    Evidence Immunofluorescence, in vitro ATM kinase assay, ATM-deficient human cells and Xenopus extracts

    PMID:11238909 PMID:11331310

    Open questions at the time
    • Downstream substrates/effectors of 53BP1 phosphorylation unknown
    • Whether foci formation requires direct chromatin binding or indirect recruitment unresolved
  2. 2003 High

    Demonstrating that 53BP1 recruitment depends on γH2AX identified the chromatin mark that seeds 53BP1 accumulation, resolving how the damage signal spreads to recruit repair factors.

    Evidence In vitro binding assay with phosphorylated/unphosphorylated H2AX; reconstitution in H2AX-deficient cells

    PMID:12697768

    Open questions at the time
    • Whether γH2AX binding is direct via the BRCT domain versus indirect via MDC1 not yet distinguished
    • Tudor domain–histone methylation recognition not yet discovered
  3. 2008 High

    Knockout studies revealed that 53BP1 promotes long-range DNA end joining during V(D)J recombination and that MDC1 acts as an intermediary between γH2AX and 53BP1, defining 53BP1's physiological role in lymphocyte genome rearrangement.

    Evidence 53BP1 KO mice with V(D)J joining defects; MDC1–53BP1 co-IP and recruitment epistasis in H2AX/MDC1-deficient cells

    PMID:18931658 PMID:18986980

    Open questions at the time
    • Mechanism of DNA end protection unknown
    • Whether 53BP1 physically prevents resection or acts indirectly unresolved
  4. 2011 High

    Discovery that MMSET-deposited H4K20me2 at DSBs recruits 53BP1, together with the finding that oligomerization and ATM phosphorylation are both needed for CSR, established that 53BP1 uses a histone-methylation-reading mechanism distinct from γH2AX and that multiple 53BP1 features cooperate in repair.

    Evidence H4K20me2 ChIP at DSBs with MMSET knockdown; 53BP1 structural mutants tested in quantitative CSR and paired-DSB joining assays

    PMID:21293379 PMID:21549309

    Open questions at the time
    • Whether H4K20me2 is read by the Tudor domain directly not structurally confirmed
    • Effector proteins downstream of 53BP1 phosphorylation not yet identified
  5. 2013 High

    Phosphomutant knock-in mice and biochemical studies separated 53BP1's effector arms: ATM-phosphorylated S/TQ sites recruit RIF1 for end-blocking while distinct sites recruit PTIP for productive CSR; concurrently, RNF168-catalyzed K63-ubiquitylation of 53BP1 was shown to be required for initial recruitment, and H4K16 acetylation was identified as an antagonist of H4K20me2 binding.

    Evidence 53BP1 phosphomutant knock-in mice with CSR/NHEJ/HR readouts; RNF168 KO ubiquitylation assays; H4K16ac chromatin fractionation and NHEJ reporter

    PMID:23329852 PMID:23727112 PMID:24324146

    Open questions at the time
    • Structural basis of dual histone-mark recognition unresolved
    • Identity of end-protection effectors downstream of RIF1 unknown
  6. 2016 High

    The cryo-EM structure of 53BP1 bound to ubiquitylated-methylated nucleosomes resolved the long-standing question of how 53BP1 simultaneously reads H4K20me2 (Tudor domain) and H2AK15ub (UDR motif), revealing selectivity determinants including arginine fingers and acidic-patch contacts.

    Evidence Cryo-EM at 4.5 Å of 53BP1 dimer on reconstituted NCP-ubme nucleosome

    PMID:27462807

    Open questions at the time
    • How higher-order oligomerization relates to foci maturation not shown structurally
    • Mechanism by which BRCA1 displaces 53BP1 in S/G2 structurally unresolved
  7. 2017 High

    Multiple regulatory layers of Tudor domain access were uncovered: TIRR was identified as a Tudor-masking protein whose dissociation is ATM-dependent; H4K20me2 dilution during replication was shown to limit 53BP1 accumulation in S phase; and competitors RNF169/RAD18 were shown to displace 53BP1 from ubiquitylated nucleosomes.

    Evidence TIRR co-IP and competition binding; crystal structure of TIRR–Tudor complex at 1.76 Å; cell-cycle H4K20me2 ChIP with EdU; NMR of RNF169/RAD18–NCP-ubme competition

    PMID:28241136 PMID:28506460 PMID:28564601 PMID:29844495

    Open questions at the time
    • Signal that releases TIRR in vivo not fully defined
    • Quantitative contribution of each gating mechanism to pathway choice not measured
  8. 2018 High

    The shieldin complex (SHLD1–SHLD2–SHLD3–REV7) and downstream CST–Polα were identified as the missing effectors that explain how 53BP1–RIF1 physically blocks end resection, with SHLD2 OB-folds binding ssDNA and Polα performing fill-in synthesis; loss of shieldin confers PARPi resistance in BRCA1-deficient cells.

    Evidence Proteomic identification; co-IP and genetic KO; ssDNA binding assays; CSR and PARPi sensitivity assays across multiple concurrent studies

    PMID:30022158 PMID:30022168 PMID:30046110

    Open questions at the time
    • Structural basis of shieldin assembly and ssDNA engagement unknown at atomic level
    • Whether CST–Polα acts at all 53BP1-dependent repair events or only CSR unclear
  9. 2018 Medium

    Additional modulators of 53BP1 chromatin occupancy were defined: CBP acetylation of the UDR motif blocks nucleosome binding (reversed by HDAC2), DYNLL1 promotes 53BP1 oligomerization, and BRCA1 inhibits ATM-dependent 53BP1 phosphorylation in S/G2 to favor HR.

    Evidence Acetylation assay and NHEJ/HR reporters; DYNLL1 KO mice with CSR assay; cell-cycle-sorted phospho-specific IF with BRCA1 domain mutants

    PMID:27462418 PMID:29190394 PMID:30559443

    Open questions at the time
    • How BRCA1 mechanistically inhibits ATM phosphorylation of 53BP1 remains unclear
    • Whether acetylation and DYNLL1 regulation are coupled not tested
  10. 2019 High

    53BP1 was shown to enforce two mechanistically separable anti-HR blocks (a pre-resection block via PTIP/S25 and a post-resection block via shieldin), and to form nuclear bodies in G1 daughters that restrain replication timing of under-replicated loci, revealing functions beyond acute DSB repair.

    Evidence 53BP1-S25A knock-in × BRCA1Δ11 mice with epistasis; live-cell replication timing analysis of 53BP1-NB-associated loci

    PMID:30804506 PMID:31653568

    Open questions at the time
    • How 53BP1-NBs sense under-replicated DNA is unknown
    • Whether the two anti-HR blocks are independently regulated in different tissues unclear
  11. 2019 High

    53BP1 liquid–liquid phase separation was shown to concentrate p53 and amplify its transcriptional response, establishing that 53BP1 foci are condensates with signaling function beyond structural scaffolding.

    Evidence OptoDroplet experiments, endogenous CRISPR tagging, osmotic/chemical perturbation, p53 target gene expression

    PMID:31267591

    Open questions at the time
    • Which phase-separation-competent domains are essential in vivo unclear
    • Relationship between LLPS and chromatin-bound oligomers not mechanistically separated
  12. 2020 High

    53BP1 was placed in a mitotic surveillance pathway with USP28 and TP53 that eliminates neural progenitor cells after prolonged mitosis; NUDT16-mediated de-ADP-ribosylation was found to stabilize 53BP1 by preventing RNF146-dependent degradation.

    Evidence Conditional triple KO mice with brain size rescue; ADP-ribosylation/ubiquitination assays with NUDT16 catalytic mutants

    PMID:31911551 PMID:33226141

    Open questions at the time
    • How 53BP1 senses prolonged mitosis mechanistically unresolved
    • Whether ADP-ribosylation regulates 53BP1 at DSBs or only governs steady-state levels unclear
  13. 2021 High

    Structural and biochemical work showed that SPOP phosphorylation by ATM induces conformational opening that enables 53BP1 polyubiquitination and VCP-mediated chromatin extraction in S phase; TIRR was further shown to block Tudor–p53-K382me2 recognition, linking TIRR to cell-fate signaling; AHNAK was identified as an oligomerization regulator controlling 53BP1 phase separation and p53 output.

    Evidence SPOP crystal structure, ubiquitination and HR assay; TIRR–Tudor–p53-K382me2 binding assay; AHNAK co-IP and phase separation assay

    PMID:33961796 PMID:33961797 PMID:34144977

    Open questions at the time
    • Cancer-derived SPOP mutations' effects on 53BP1-dependent repair in patient tumors not validated
    • How AHNAK itself is regulated during DSB signaling unknown
  14. 2022 High

    The structural code for RIF1 recruitment was resolved: RIF1 is a phosphopeptide-binding protein recognizing three LxL-phospho motifs in 53BP1, with an alternative shieldin recruitment mode providing redundancy; 53BP1 was also shown to phase-separate with HP1α at heterochromatin to maintain repeat silencing.

    Evidence Phosphopeptide binding assay with mutagenesis and CSR; LLPS assay with CRISPR KO and repeat RNA expression

    PMID:35042897 PMID:35216668

    Open questions at the time
    • Structural basis of full-length RIF1–53BP1 complex not determined
    • Whether heterochromatin LLPS function is independent of DSB repair in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of 53BP1 higher-order oligomerization at DSBs; how 53BP1 senses prolonged mitosis in the surveillance pathway; whether distinct post-translational modifications (ADP-ribosylation, methylation, acetylation) cooperate or act in separate contexts; and the full mechanism by which BRCA1 inhibits ATM-dependent 53BP1 phosphorylation.
  • No high-resolution structure of full-length 53BP1 oligomer on chromatin
  • Mitotic surveillance sensing mechanism unknown
  • Integrated PTM code for 53BP1 not systematically tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 5 GO:0060090 molecular adaptor activity 5
Localization
GO:0005654 nucleoplasm 3 GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 7 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 1
Partners
AHNAKDYNLL1PTIPREV7RIF1SHLD2TIRRTOPBP1
Complex memberships
53BP1-RIF1-shieldin (SHLD1-SHLD2-SHLD3-REV7)53BP1-TIRR

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 53BP1 becomes hyperphosphorylated and forms discrete nuclear foci in response to DNA damage; ATM-deficient cells show no 53BP1 hyperphosphorylation and reduced foci formation; 53BP1 is phosphorylated by ATM in vitro, establishing 53BP1 as an ATM substrate in DNA damage signaling. Immunofluorescence, in vitro kinase assay, ATM-deficient cell lines, wortmannin inhibition The Journal of cell biology High 11331310
2001 53BP1 localizes to chromatin and forms nuclear foci upon DNA damage; Xenopus 53BP1 is hyperphosphorylated after X-ray irradiation in an ATM kinase-dependent manner; inhibitors of ATM-related kinases delay relocalization and reduce phosphorylation of 53BP1. Live cell imaging, immunofluorescence, X-irradiation, ATM kinase inhibitors, AT cells Molecular and cellular biology High 11238909
2003 A region upstream of the 53BP1 C-terminus is required and sufficient for recruitment to DNA break sites by directly binding phosphorylated H2AX (γH2AX) but not unphosphorylated H2AX; H2AX phosphorylation at serine 140 is critical for 53BP1 foci formation; ATM-mediated N-terminal phosphorylation of 53BP1 is not required for its relocalization. In vitro binding assay, H2AX-deficient cell reconstitution with wild-type or phospho-deficient H2AX, domain mapping The Journal of biological chemistry High 12697768
2008 53BP1 facilitates long-range DNA end-joining during V(D)J recombination; 53BP1-deficient lymphocytes show impaired distal V-DJ joining with extensive degradation of unrepaired coding ends, demonstrating a role in genomic stability during long-range joining of DNA breaks distinct from classical NHEJ. 53BP1 knockout mouse model, V(D)J recombination assay, genomic analysis of TCR locus Nature High 18931658
2008 53BP1 and MDC1 interact directly through the tandem BRCT domain of MDC1 and residues 1288–1409 of 53BP1; this interaction is required for recruitment of 53BP1 to DSB sites; after DSB induction, the interaction is reduced due to competition between γH2AX and 53BP1 for MDC1 BRCT domain binding; the interaction is enhanced during mitosis in a phospho-dependent manner. Co-IP, pulldown, domain mapping, immunofluorescence in H2AX-deficient and MDC1-deficient cells The Journal of biological chemistry High 18986980
2009 PTIP regulates 53BP1 localization to DNA damage sites downstream of RNF8; PTIP depletion prevents 53BP1 foci formation; SMC1 phosphorylation at DSB sites is dependent on PTIP, placing PTIP between RNF8 and 53BP1 in the DNA damage signaling pathway. siRNA knockdown, co-IP, immunofluorescence, epistasis analysis The Journal of biological chemistry Medium 19414588
2009 Protein phosphatase 5 (PP5) binds 53BP1 and dephosphorylates it at Ser-25 and Ser-1778 after DNA damage; PP5 overexpression accelerates 53BP1 dephosphorylation and reduces phospho-53BP1 foci; PP5 downregulation inhibits dephosphorylation, prolonging foci; PP5 overexpression reduces NHEJ activity. Yeast two-hybrid, co-IP, overexpression/knockdown in U2OS cells, NHEJ reporter assay The Journal of biological chemistry Medium 19176521
2010 TopBP1 colocalizes with 53BP1 at DSBs in G1 phase; TopBP1 BRCT domains 4-5 interact with 53BP1; recruitment of TopBP1 to DSBs in G1 is dependent on 53BP1; loss of TopBP1 or 53BP1 causes G1 DNA damage checkpoint defects. Co-IP, siRNA knockdown, immunofluorescence, G1 checkpoint assay (S-phase entry after irradiation) The EMBO journal High 20871591
2011 53BP1 facilitates joining of intrachromosomal DSBs only at distances corresponding to γH2AX spreading (~1 Mb); DNA end protection by 53BP1 is distance-independent; chromatin association, oligomerization, and N-terminal ATM phosphorylation of 53BP1 are all required for DNA end protection and CSR. Paired DSB joining assay across chromosomal distances, 53BP1 mutant analysis, class switch recombination assay Molecular cell High 21549309
2011 MMSET (NSD2/WHSC1) is recruited to DSBs via the γH2AX-MDC1 pathway (MDC1 BRCT domain binds phospho-Ser102 of MMSET) and locally methylates H4K20 at DSBs; this local increase in H4K20me2 is required for 53BP1 recruitment; MMSET knockdown significantly decreases H4K20me2 at DSBs and subsequent 53BP1 accumulation. ChIP, siRNA knockdown, co-IP, immunofluorescence, H4K20 methylation assay Nature High 21293379
2013 53BP1 promotes productive CSR and suppresses mutagenic DNA repair through distinct phosphodependent interactions: ATM-mediated phosphorylation of S/TQ sites recruits RIF1 (via 8 N-terminal sites) for end-blocking, while separate phosphorylation recruits PTIP for CSR; a 53BP1-8A phosphomutant recruits RIF1 but not PTIP. 53BP1 phosphomutant knock-in mice, CSR assay, immunofluorescence, co-IP Cell High 23727112
2013 53BP1 phase separates to form liquid-like repair compartments at DSBs; 53BP1 assembly is sensitive to osmotic pressure, temperature, salt, and hydrophobic interactions; p53 is enriched within 53BP1 optoDroplets; disruption of 53BP1 phase separation impairs p53 induction and p53 target gene expression. Live cell microscopy, CRISPR endogenous tagging, optoDroplet experiments, osmotic/chemical perturbations The EMBO journal High 31267591
2013 RNF168 mediates K63-linked ubiquitylation of 53BP1, which is required for initial recruitment of 53BP1 to DSBs and for its function in DNA repair, checkpoint activation, and genomic integrity. Ubiquitylation assay, co-IP, RNF168 KO/KD cells, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 24324146
2013 H4K16 acetylation antagonizes 53BP1 binding to H4K20me2; DNA damage induces transient, localized H4 deacetylation at DSBs which facilitates 53BP1 foci formation and NHEJ; 53BP1 foci assemble primarily on H4K20me2 established by SETD8 and SUV420 methyltransferases, not de novo MMSET-mediated methylation. Chromatin fractionation, siRNA knockdown of methyltransferases/HDAC, NHEJ reporter, immunofluorescence Journal of molecular cell biology Medium 23329852
2014 53BP1 tandem Tudor domain binds methylated K810 of pRb; structural elucidation reveals recognition of the methylated lysine and surrounding residues; 53BP1 binding to methyl-K810 pRb occurs at E2F target genes, integrating pRb activity with the DNA damage response. Structural biology (crystal structure), binding assay, ChIP Proceedings of the National Academy of Sciences of the United States of America High 25049398
2014 UbcH7 (Ube2L3) regulates steady-state and replication stress-induced ubiquitination and proteasome-dependent degradation of 53BP1; N-terminal phosphorylation of 53BP1 is involved in replication stress-induced degradation; UbcH7 depletion stabilizes 53BP1, inhibits DSB end resection, increases NHEJ and decreases HR. shRNA screen, ubiquitination assay, NHEJ/HR reporter, immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America Medium 25422456
2014 ATM-dependent MOF phosphorylation at T392 colocalizes with 53BP1 at DSBs; MOF-T392A mutation blocks reduction of DSB-associated 53BP1 in S/G2 phase, enhances 53BP1 and reduces BRCA1 at DSBs, and impairs HR repair. Phospho-mutant expression, immunofluorescence, co-IP, HR reporter assay Cell reports Medium 24953651
2015 Chemical proteomics identified 53BP1 as a direct γH2AX binder through its BRCT domains; a 53BP1 mutant deficient in γH2AX binding shows altered localization to chromosomal breaks, revealing that direct γH2AX recognition by the BRCT domains modulates 53BP1 localization at damage sites. Quantitative chemical proteomics (γH2AX affinity pulldown from native proteome), mutant localization assay Nature chemical biology High 26344695
2015 BRCA1 inhibits ATM-dependent 53BP1 phosphorylation in S/G2 phases, restricting RIF1 and PTIP accumulation at DSBs to G1; both BRCT and RING domains of BRCA1 are required for inhibition of 53BP1 phosphorylation, ensuring HR predominates in S/G2. Cell cycle-sorted cells, phospho-specific antibodies, immunofluorescence, BRCA1 domain mutants Cell discovery Medium 27462418
2016 Cryo-EM structure of dimerized human 53BP1 bound to H4K20me2- and H2AK15ub-containing nucleosome (NCP-ubme) at 4.5 Å; reveals simultaneous engagement of H4K20me2 by tandem Tudor domain and H2AK15ub by UDR motif; ubiquitin is sandwiched between UDR and NCP surface; two arginine fingers in H2A tail position ubiquitin and confer selectivity for H2AK15ub over H2AK13ub; intimate contacts with the nucleosomal acidic patch are required. Cryo-EM structure determination at 4.5 Å, biochemical validation Nature High 27462807
2016 Silencing 53BP1 or exhausting its chromatin-binding capacity switches DSB repair from error-free gene conversion (RAD51) to mutagenic single-strand annealing (RAD52), demonstrating that 53BP1 fosters fidelity of HDR rather than simply suppressing it. siRNA knockdown, HR sub-pathway reporter assays, RAD51/RAD52 focus formation Nature structural & molecular biology Medium 27348077
2017 TIRR directly binds the tandem Tudor domain of 53BP1 and masks its H4K20me2 binding motif, preventing 53BP1 recruitment to DSBs; ATM phosphorylation of 53BP1 after DNA damage recruits RIF1 and dissociates the 53BP1-TIRR complex; TIRR overexpression impedes 53BP1 function; TIRR depletion destabilizes soluble 53BP1. Co-IP, pulldown, immunofluorescence, ATM inhibition, Tudor domain binding competition assay Nature High 28241136
2017 Crystal structure of TIRR in complex with 53BP1 tandem Tudor domain at 1.76 Å; N-terminal region (residues 10-24) and L8-loop of TIRR interact with 53BP1 Tudor through loops L1, L3, and L1'; TIRR histidine H106 is essential for 53BP1 Tudor binding; TIRR recognition blocks H4K20me2 binding. X-ray crystallography, NMR, mutagenesis, in vivo functional assays Nature communications High 29844495
2017 NMR and biochemistry reveal that RNF169 bridges ubiquitin and histone surfaces on NCP-ubme with high affinity (conformational selection), displacing low-affinity 53BP1 from H2AK15ub nucleosomes; RAD18 also binds NCP-ubme through a ubiquitin-binding domain that contacts sites accessed by 53BP1, providing an alternative mechanism for 53BP1 displacement. NMR spectroscopy, biochemical binding assay, competition assays with reconstituted nucleosomes Molecular cell High 28506460
2017 53BP1 accumulation at DSBs declines as cells progress through S phase due to replication-coupled dilution of H4K20me2; premature maturation of post-replicative chromatin restores H4K20me2 and rescues 53BP1 accumulation, establishing that H4K20me2 availability controls 53BP1-mediated repair pathway choice across the cell cycle. Live cell imaging, cell cycle synchronization, H4K20me2 ChIP, EdU labeling Cell reports High 28564601
2017 An engineered ubiquitin variant (i53) blocks 53BP1 accumulation at DSBs by inhibiting its UDR/Tudor-mediated chromatin recruitment, increasing HDR-dependent genome editing by up to 5.6-fold, confirming that 53BP1 suppresses end resection as a key step in HDR. Ubiquitin variant library screen, CRISPR-Cas9 HDR assay, immunofluorescence Nature biotechnology High 29176614
2018 Shieldin complex (SHLD1/C20orf196, SHLD2/FAM35A, SHLD3/CTC-534A2.2, REV7) is a 53BP1 effector that localizes to DSBs in a 53BP1- and RIF1-dependent manner; SHLD2 binds single-stranded DNA via OB-fold domains; loss of shieldin impairs NHEJ, immunoglobulin class switching, causes hyper-resection, and confers PARP inhibitor resistance in BRCA1-deficient cells. Proteomics/MS, co-IP, genetic KO, immunofluorescence, ssDNA binding assay, CSR assay, PARPi sensitivity Nature High 30022168
2018 CST (CTC1-STN1-TEN1) interacts with shieldin downstream of 53BP1-RIF1; CST and Polα localize to DNA damage sites in a 53BP1- and shieldin-dependent manner; CST-Polα-mediated fill-in controls DSB repair by limiting resection; CST depletion increases resection and, in BRCA1-deficient cells, blocks RAD51 loading and diminishes PARPi efficacy. Co-IP, immunofluorescence, siRNA knockdown, resection assays, RAD51 focus formation, PARPi sensitivity Nature High 30022158
2018 53BP1 cooperates with REV7 to promote NHEJ during CSR, while REV7 is dispensable for 53BP1-dependent V(D)J recombination; shieldin (REV7-SHLD1-SHLD2-SHLD3) explains this DNA structure specificity by mediating end-protection in ssDNA compartments and is essential for REV7-dependent NHEJ in CSR but dispensable for REV7-dependent interstrand crosslink repair. Mouse genetics (conditional KO), CSR assay, V(D)J recombination analysis, shieldin identification by proteomics Nature High 30046110
2018 DYNLL1 directly binds 53BP1 and stimulates 53BP1 oligomerization, promoting 53BP1 recruitment and interaction with DSB-associated chromatin; loss of DYNLL1 or its transcriptional regulator ASCIZ impairs CSR and renders BRCA1-mutant tumors resistant to PARP inhibitors. Co-IP, pulldown, immunofluorescence, DYNLL1 KO mice, CSR assay, PARPi sensitivity assay Nature communications High 30559443
2018 CBP-mediated acetylation of 53BP1 at K1626/K1628 in the UDR motif disrupts interaction between 53BP1 and nucleosomes, blocking recruitment of 53BP1, PTIP, and RIF1 to DSBs and shifting repair toward HR; HDAC2 reverses this acetylation to maintain NHEJ/HR balance. Co-IP, immunofluorescence, acetylation assay, NHEJ/HR reporter, HDAC2 knockdown Nucleic acids research Medium 29190394
2018 GFI1 interacts with PRMT1 and enables PRMT1 to bind and methylate 53BP1 (and MRE11), which is necessary for 53BP1 function in the DNA damage response; GFI1 deletion causes hypersensitivity to ionizing radiation and DNA repair defects. Co-IP, methylation assay, GFI1 KO, immunofluorescence, clonogenic survival Nature communications Medium 29651020
2019 53BP1 enforces two distinct anti-HR blocks: (1) a pre-resection block via PTIP interaction (S25 phosphorylation site) controlling DNA2-dependent end resection, and (2) a post-resection block via shieldin that inhibits RNF168-mediated PALB2/RAD51 loading onto ssDNA. 53BP1-S25A knock-in mice crossed with BRCA1Δ11 mice, RAD51/PALB2 focus formation, PARPi sensitivity, epistasis analysis Molecular cell High 31653568
2019 53BP1 nuclear bodies (53BP1-NBs) in G1 daughter cells restrain replication of embedded under-replicated DNA loci until late S phase, enabling RAD52-mediated repair; absence or malfunction of 53BP1-NBs causes premature replication of affected loci and genotoxic RAD51-mediated recombination. Live cell imaging, CRISPR labeling, EdU incorporation, RAD52/RAD51 focus assay, replication timing analysis Nature cell biology High 30804506
2019 TOPBP1 BRCT domains selectively bind conserved phosphorylation sites in the N-terminus of 53BP1; mutation of these sites abolishes TOPBP1, ATR, and CHK1 recruitment to 53BP1 damage foci and abrogates G1 cell cycle arrest; TOPBP1 interaction with 53BP1 is structurally complementary to its interaction with RAD9-RAD1-HUS1, allowing simultaneous binding and cooperation in ATR activation. Structural analysis, phospho-mutant analysis, co-IP, G1 checkpoint assay, immunofluorescence eLife High 31135337
2019 TPX2/Aurora A heterodimer is a novel 53BP1 binding partner; TPX2/Aurora A counteracts 53BP1 function to promote DNA end resection, BRCA1/Rad51 recruitment, and HR; loss of TPX2 or Aurora A causes deprotection of stalled replication forks in an MRE11-dependent manner; concurrent 53BP1 loss rescues BRCA1/Rad51 recruitment and fork instability. Co-IP (MS), immunofluorescence, siRNA knockdown, replication fork protection assay, HR assay The Journal of cell biology Medium 30602538
2019 LC8 (DYNLL1) accumulates at laser-induced DNA damage tracks in a 53BP1-dependent manner, requiring the H2AX-MDC1-RNF8-RNF168 cascade; genetic inactivation of LC8 or its interaction with 53BP1 causes checkpoint defects; LC8 loss alleviates hypersensitivity of BRCA1-depleted cells to IR and PARP inhibition. Laser micro-irradiation, co-IP, LC8 genetic inactivation, checkpoint assay, PARPi sensitivity Nucleic acids research Medium 30982887
2019 Preformed 53BP1 dimers relocate from the nucleoplasm to DSB sites; at DSBs, consecutive recognition of H2AK15ub and H4K20me2 leads to assembly of 53BP1 oligomers and a mature foci structure, as quantified in living cells by fluorescence fluctuation spectroscopy. Fluorescence fluctuation spectroscopy (FFS), AsiSI-inducible DSB system, live-cell imaging Nature communications High 33188174
2020 53BP1 localizes to replication forks following induced replication stress and is required for normal ATR-Chk1-p53 signaling; absence of 53BP1 leads to defective ATR-Chk1 signaling, caspase 3-mediated cell death, and degradation of nascent replicated DNA in early S-phase B cells. 53BP1-/- primary B cells, replication fork labeling (EdU/BrdU), Chk1 phosphorylation assay, caspase activation Molecular and cellular biology Medium 29378830
2020 PRMT5 methylates and stabilizes 53BP1 to promote NHEJ; Src kinase phosphorylates PRMT5 at Y324, suppressing PRMT5 methyltransferase activity and preventing 53BP1 methylation; Src-mediated inhibition of PRMT5 during DNA damage blocks NHEJ and leads to apoptosis. In vitro methylation assay, co-IP, phospho-mutant analysis, NHEJ reporter, apoptosis assay Communications biology Medium 32759981
2020 NUDT16 regulates 53BP1 stability by reversing ADP-ribosylation; ADP-ribosylated 53BP1 is targeted by RNF146 for polyubiquitination and degradation; NUDT16 catalytic activity is required for 53BP1 de-ADP-ribosylation, stability, and localization at DSBs. ADP-ribosylation assay, ubiquitination assay, co-IP, NUDT16 catalytic mutant, immunofluorescence Cancer research Medium 31911551
2020 Centrosome loss in neural progenitor cells prolongs mitosis and activates a 53BP1-USP28-TP53 mitotic surveillance pathway causing apoptosis; deletion of 53BP1 or USP28 restores NPC proliferation and brain size without correcting upstream centrosome defects, establishing 53BP1 as a required component of this pathway. Conditional KO mouse models, brain size measurement, mitotic timing assay, apoptosis assay The EMBO journal High 33226141
2021 ATM-phosphorylated SPOP undergoes a conformational change (revealed by crystal structure) that stabilizes its interaction with 53BP1; SPOP induces polyubiquitination of 53BP1, causing VCP/p97-mediated extraction of 53BP1 from chromatin during S phase, thus promoting HR over NHEJ; cancer-derived SPOP mutations block this interaction. X-ray crystal structure of SPOP, co-IP, ubiquitination assay, SPOP mutant analysis, HR/NHEJ reporter Science advances High 34144977
2021 AHNAK binds the 53BP1 oligomerization domain in G1 phase and controls 53BP1 multimerization; loss of AHNAK leads to hyper-accumulation of 53BP1 on chromatin and enhanced phase separation, culminating in elevated p53 response. Co-IP, fluorescence microscopy, phase separation assay, p53 target gene expression, siRNA/KO Molecular cell High 33961796
2021 TIRR inhibits formation of the 53BP1 Tudor domain-p53 K382me2 complex; loss of TIRR causes aberrant increases in p53 transactivation; TIRR binds the Tudor domain and blocks p53 dimethyl-lysine recognition, linking TIRR to cell-fate decisions beyond DSB repair. Co-IP, Tudor domain-p53 binding assay (methylated K382 peptide), p53 target gene expression, TIRR KO Molecular cell High 33961797
2021 Lamin B1 directly interacts with 53BP1 and sequesters it from DSB sites; lamin B1 overexpression impedes 53BP1 recruitment to DNA damage, causes persistence of DNA damage, and defects in NHEJ; the interaction is dissociated after DNA damage. Co-IP, pulldown, immunofluorescence, NHEJ reporter, DSB sensitivity assay Science advances Medium 34452908
2021 AMPK directly phosphorylates 53BP1 at Ser1317 in response to DSBs; this phosphorylation promotes 53BP1 recruitment to DSBs and efficient classical NHEJ (c-NHEJ), maintaining genomic stability and immune repertoire diversity. In vitro kinase assay (AMPK-53BP1), co-IP, phospho-mutant analysis, immunofluorescence, CSR assay Cell reports Medium 33596428
2021 ATM phosphorylates ESCO2 at S196 and T233; MDC1 recognizes phosphorylated ESCO2 and recruits it to DSBs; ESCO2-mediated SMC3 acetylation stabilizes cohesin complex conformation and regulates chromatin structure at DSBs, which is essential for 53BP1 recruitment and formation of 53BP1 microdomains. Co-IP, acetylation assay, siRNA knockdown, immunofluorescence, ESCO2 KO cells/xenograft Nucleic acids research Medium 37377435
2022 53BP1 undergoes liquid-liquid phase separation with HP1α at heterochromatin in a mutually dependent manner; 53BP1 deletion reduces heterochromatin centers and de-represses tandem repetitive DNA; domains required for LLPS at heterochromatin overlap with but are distinct from those for DSB repair. LLPS assay, CRISPR KO, immunofluorescence, repeat RNA expression assay, domain deletion analysis Nature communications Medium 35042897
2022 RIF1 is a phosphopeptide-binding protein that directly interacts with three phosphorylated 53BP1 epitopes sharing an LxL motif followed by two closely apposed phosphorylated residues; simultaneous mutation of these sites abrogates RIF1 IRIF but only fully compromises repair when an alternative shieldin recruitment mode is also disabled; RIF1 also modifies shieldin action independently of 53BP1 binding. Phosphopeptide binding assay, mutagenesis, co-IP, immunofluorescence (IRIF), CSR assay Molecular cell High 35216668
2023 SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thereby reducing DNA repair at DSBs. SARS-CoV-2 infection of cells and mice, 53BP1 foci quantification, lncRNA perturbation assay Nature cell biology Medium 36894671

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Double-strand break repair: 53BP1 comes into focus. Nature reviews. Molecular cell biology 868 24326623
2018 The shieldin complex mediates 53BP1-dependent DNA repair. Nature 500 30022168
2001 Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways. The Journal of cell biology 418 11331310
2019 Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments. The EMBO journal 358 31267591
2018 53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in. Nature 350 30022158
2011 MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites. Nature 334 21293379
2013 53BP1: pro choice in DNA repair. Trends in cell biology 302 24094932
2003 Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. The Journal of biological chemistry 301 12697768
2001 Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage. Molecular and cellular biology 300 11238909
2013 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 292 23727112
2008 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature 260 18931658
2018 53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ. Nature 252 30046110
2016 The structural basis of modified nucleosome recognition by 53BP1. Nature 201 27462807
2011 Regulation of DNA end joining, resection, and immunoglobulin class switch recombination by 53BP1. Molecular cell 198 21549309
2017 Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR-Cas9 genome-editing efficiency. Nature biotechnology 197 29176614
2016 53BP1 fosters fidelity of homology-directed DNA repair. Nature structural & molecular biology 185 27348077
2020 53BP1: a DSB escort. Genes & development 175 31896689
1996 The interferon-inducible p202 protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities. Molecular and cellular biology 142 8524315
2007 Cytoplasmic irradiation induces mitochondrial-dependent 53BP1 protein relocalization in irradiated and bystander cells. Cancer research 133 17575156
2013 Histone H4 deacetylation facilitates 53BP1 DNA damage signaling and double-strand break repair. Journal of molecular cell biology 128 23329852
2013 Role of 53BP1 in the regulation of DNA double-strand break repair pathway choice. Radiation research 121 24320053
2017 TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature 110 28241136
2018 53BP1: A key player of DNA damage response with critical functions in cancer. DNA repair 105 30497961
1995 Binding of an interferon-inducible protein (p202) to the retinoblastoma protein. The Journal of biological chemistry 105 7890747
2017 Replication-Coupled Dilution of H4K20me2 Guides 53BP1 to Pre-replicative Chromatin. Cell reports 103 28564601
2019 53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination. Molecular cell 100 31653568
1996 Inhibition of E2F-mediated transcription by p202. The EMBO journal 95 8896460
2023 SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. Nature cell biology 94 36894671
2015 Chemical proteomics reveals a γH2AX-53BP1 interaction in the DNA damage response. Nature chemical biology 93 26344695
2018 The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity. Nature communications 87 30559443
2019 53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage. Nature cell biology 86 30804506
2022 53BP1 regulates heterochromatin through liquid phase separation. Nature communications 85 35042897
2020 Roles for 53BP1 in the repair of radiation-induced DNA double strand breaks. DNA repair 85 33087281
2013 RNF168 ubiquitylates 53BP1 and controls its response to DNA double-strand breaks. Proceedings of the National Academy of Sciences of the United States of America 85 24324146
2011 BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability. Journal of molecular cell biology 84 21278454
2014 MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice. Cell reports 81 24953651
2005 ATM signaling and 53BP1. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 81 16024119
2021 Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps. Molecular cell 77 34555355
2017 Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin Recruitment by RNF168/169 and RAD18. Molecular cell 76 28506460
2010 TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint. The EMBO journal 76 20871591
2013 Molecular mechanism for p202-mediated specific inhibition of AIM2 inflammasome activation. Cell reports 74 23850291
2018 BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance. Cell reports 70 30257212
2006 53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis. Proceedings of the National Academy of Sciences of the United States of America 66 16492765
2021 AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. Molecular cell 65 33961796
2017 53BP1 and BRCA1 control pathway choice for stalled replication restart. eLife 65 29106372
1997 Inhibition of E2F-4/DP-1-stimulated transcription by p202. Oncogene 65 9233764
2001 The gene encoding p202, an interferon-inducible negative regulator of the p53 tumor suppressor, is a target of p53-mediated transcriptional repression. The Journal of biological chemistry 64 11013253
2015 Cell cycle-dependent inhibition of 53BP1 signaling by BRCA1. Cell discovery 62 27462418
2018 53BP1 Mediates ATR-Chk1 Signaling and Protects Replication Forks under Conditions of Replication Stress. Molecular and cellular biology 61 29378830
2021 Oncogenic KRAS drives radioresistance through upregulation of NRF2-53BP1-mediated non-homologous end-joining repair. Nucleic acids research 57 34606602
2020 PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation. Communications biology 56 32759981
2020 Centrosome defects cause microcephaly by activating the 53BP1-USP28-TP53 mitotic surveillance pathway. The EMBO journal 53 33226141
2018 GFI1 facilitates efficient DNA repair by regulating PRMT1 dependent methylation of MRE11 and 53BP1. Nature communications 52 29651020
2002 Interferon-inducible p202 in the susceptibility to systemic lupus. Frontiers in bioscience : a journal and virtual library 52 11991834
2008 The direct interaction between 53BP1 and MDC1 is required for the recruitment of 53BP1 to sites of damage. The Journal of biological chemistry 51 18986980
2019 Mitotic regulators TPX2 and Aurora A protect DNA forks during replication stress by counteracting 53BP1 function. The Journal of cell biology 49 30602538
2018 Acetylation of 53BP1 dictates the DNA double strand break repair pathway. Nucleic acids research 48 29190394
2024 Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology 47 38244928
2021 ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication. Science advances 47 34144977
2017 Frameshift Mutations in Repeat Sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 Genes in Colon Cancers. Pathology oncology research : POR 47 28803425
2019 Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint. eLife 46 31135337
2022 Multifaceted regulation and functions of 53BP1 in NHEJ‑mediated DSB repair (Review). International journal of molecular medicine 45 35583003
2018 RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair. Proceedings of the National Academy of Sciences of the United States of America 45 30104380
2018 Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR. Nature communications 44 29844495
2012 Discordance between phosphorylation and recruitment of 53BP1 in response to DNA double-strand breaks. Cell cycle (Georgetown, Tex.) 42 22421153
2021 Lamin B1 sequesters 53BP1 to control its recruitment to DNA damage. Science advances 41 34452908
2018 H4K20me2 distinguishes pre-replicative from post-replicative chromatin to appropriately direct DNA repair pathway choice by 53BP1-RIF1-MAD2L2. Cell cycle (Georgetown, Tex.) 41 29160738
2018 53BP1 can limit sister-chromatid rupture and rearrangements driven by a distinct ultrafine DNA bridging-breakage process. Nature communications 41 29445165
2009 PTIP regulates 53BP1 and SMC1 at the DNA damage sites. The Journal of biological chemistry 41 19414588
2014 Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor. Proceedings of the National Academy of Sciences of the United States of America 40 25049398
2014 UbcH7 regulates 53BP1 stability and DSB repair. Proceedings of the National Academy of Sciences of the United States of America 40 25422456
2019 LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic acids research 39 30982887
2008 RNF8-dependent and RNF8-independent regulation of 53BP1 in response to DNA damage. The Journal of biological chemistry 39 18337245
2022 BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1. Nature communications 38 35017534
2021 DSB repair pathway choice is regulated by recruitment of 53BP1 through cell cycle-dependent regulation of Sp1. Cell reports 37 33730584
2020 Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break. Nature communications 37 33188174
2020 CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks. Nature communications 36 33188175
1999 Reduced growth rate and transformation phenotype of the prostate cancer cells by an interferon-inducible protein, p202. Oncogene 36 9989832
2000 Tumor suppression and sensitization to tumor necrosis factor alpha-induced apoptosis by an interferon-inducible protein, p202, in breast cancer cells. Cancer research 35 10646849
2022 RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1. Molecular cell 34 35216668
2020 Nudix Hydrolase NUDT16 Regulates 53BP1 Protein by Reversing 53BP1 ADP-Ribosylation. Cancer research 33 31911551
2018 H3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions. Aging 33 30312172
2023 DNA damage-induced cellular senescence is regulated by 53BP1 accumulation in the nuclear foci and phase separation. Cell proliferation 32 36642815
2022 53BP1: Keeping It under Control, Even at a Distance from DNA Damage. Genes 32 36553657
2001 p202, an interferon-inducible protein, mediates multiple antitumor activities in human pancreatic cancer xenograft models. Cancer research 32 11585747
2021 AMPK-mediated phosphorylation on 53BP1 promotes c-NHEJ. Cell reports 30 33596428
2019 The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair. Nucleic acids research 30 30812030
2009 Protein phosphatase 5 regulates the function of 53BP1 after neocarzinostatin-induced DNA damage. The Journal of biological chemistry 30 19176521
2021 TIRR inhibits the 53BP1-p53 complex to alter cell-fate programs. Molecular cell 28 33961797
2017 γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget 28 28969073
2017 Around and beyond 53BP1 Nuclear Bodies. International journal of molecular sciences 28 29206178
1999 Retardation of cell proliferation after expression of p202 accompanies an increase in p21(WAF1/CIP1). Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 28 10074903
2022 Individual radiosensitivity reflected by γ-H2AX and 53BP1 foci predicts outcome in PSMA-targeted radioligand therapy. European journal of nuclear medicine and molecular imaging 27 36136101
2017 Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer. Molecular cancer therapeutics 27 28958991
2020 Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases. Nature communications 26 32576832
2023 ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex. Nucleic acids research 25 37377435
2015 Functional crosstalk between DNA damage response proteins 53BP1 and BRCA1 regulates double strand break repair choice. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 25 26615718
2001 p202, an interferon-inducible negative regulator of cell growth, is a target of the adenovirus E1A protein. Oncogene 25 11687962
2017 DNA Damage Detection by 53BP1: Relationship to Species Longevity. The journals of gerontology. Series A, Biological sciences and medical sciences 24 27573809
2015 Ectopic expression of RNF168 and 53BP1 increases mutagenic but not physiological non-homologous end joining. Nucleic acids research 24 25916843