Affinage

TOPBP1

DNA topoisomerase 2-binding protein 1 · UniProt Q92547

Length
1522 aa
Mass
170.7 kDa
Annotated
2026-04-28
100 papers in source corpus 55 papers cited in narrative 55 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOPBP1 is a multi-BRCT-domain scaffold protein that serves as the principal activator of ATR checkpoint kinase signaling and an essential platform for DNA replication initiation, DNA repair, and mitotic genome stability. Its intrinsically disordered ATR-activation domain (AAD) directly stimulates ATR-ATRIP kinase activity, and this activation is amplified by liquid-liquid phase separation of TOPBP1 into condensates; AAD function is essential for viability, as a W1147R knock-in is embryonic lethal in mice (PMID:16530042, PMID:33503405, PMID:23950734). TOPBP1 is recruited to damaged or stalled replication forks through phospho-dependent interactions mediated by its tandem BRCT domains—BRCT1-2 binds CK2-phosphorylated Rad9 (9-1-1 clamp), BRCT4-5 binds 53BP1 for the G1 checkpoint, and BRCT7-8 binds BACH1/FANCJ—while CDK-phosphorylated Treslin/TICRR engages BRCT3-4 to trigger replication origin firing (PMID:26724438, PMID:30295604, PMID:20116089, PMID:31135337). Beyond checkpoint and replication roles, Akt phosphorylation at Ser-1159 drives TOPBP1 oligomerization via BRCT7-8, switching its function from ATR activation to E2F1 transcriptional repression, and during mitosis TOPBP1 forms CIP2A–MDC1-dependent filamentous structures that tether DSBs to prevent chromosome mis-segregation (PMID:24081328, PMID:30898438, PMID:35842428).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 Medium

    Initial characterization established TOPBP1 as a replication-associated protein that interacts with DNA polymerase epsilon, BRCA1, and Rad9, placing it at the intersection of replication and DNA damage responses.

    Evidence Co-immunoprecipitation and colocalization at replication foci in human cells

    PMID:11395493

    Open questions at the time
    • No enzymatic activity identified
    • Mechanism of action at replication forks unknown
    • Functional significance of individual interactions not tested
  2. 2003 Medium

    TOPBP1 was found to directly interact with E2F1 via its sixth BRCT domain and repress E2F1-dependent transcription and apoptosis after DNA damage, revealing an unexpected transcriptional regulatory role beyond replication.

    Evidence Co-immunoprecipitation, domain-mapping, transcriptional reporter assays in human cells; Brg1/Brm chromatin remodeler recruitment shown by ChIP

    PMID:12697828 PMID:15075294

    Open questions at the time
    • Physiological significance of E2F1 repression versus checkpoint function unclear
    • No structural basis for E2F1 recognition
  3. 2006 High

    The landmark discovery that TOPBP1 directly activates ATR-ATRIP kinase through a conserved AAD between BRCT domains VI and VII established TOPBP1 as the primary ATR activator, resolving how ATR is stimulated at DNA damage sites.

    Evidence Recombinant protein kinase assays, point mutagenesis (W1145R), Xenopus egg extract complementation, and RNAi in human cells

    PMID:16530042 PMID:16880517

    Open questions at the time
    • Structural basis of AAD–ATR interaction unknown
    • Whether additional ATR activators exist was unresolved
  4. 2007 High

    The mechanism linking the 9-1-1 clamp to ATR activation was resolved: phosphorylated Rad9 tail recruits TOPBP1 BRCT1-2 to stalled forks, and bypass experiments (AAD fused to PCNA/H2B) proved that 9-1-1's primary role is spatial localization of the AAD.

    Evidence Co-IP with phosphopeptides, domain fusion constructs bypassing 9-1-1, checkpoint assays in Xenopus extracts and human cells

    PMID:17575048 PMID:17636252

    Open questions at the time
    • Structural detail of BRCT1-2/Rad9-pSer387 interface not yet solved
    • Contribution of additional recruiters (MRN, MDC1) not yet dissected
  5. 2007 High

    ATM-mediated phosphorylation of TOPBP1 at Ser-1131 was shown to enhance ATR-ATRIP binding specifically after DSBs, establishing a direct signaling cross-talk between ATM and ATR pathways through TOPBP1.

    Evidence Phosphospecific antibodies, in vitro ATM kinase assays, phospho-mutant rescue in Xenopus egg extracts

    PMID:17446169

    Open questions at the time
    • Whether this phosphorylation event occurs in human cells not directly shown
    • Mechanism by which pS1131 enhances ATR binding unresolved
  6. 2008 High

    The NBS1-TOPBP1 BRCT interaction was identified as the bridge enabling ATM to phosphorylate and activate TOPBP1 at DSBs, while ATR's PRD and ATRIP's TOPBP1-interaction region were mapped as the direct contact surfaces required for AAD-mediated activation.

    Evidence Co-IP in egg extracts with NBS1 depletion/BRCT mutants; domain mutagenesis of ATR PRD and ATRIP in kinase assays and cellular complementation

    PMID:18519640 PMID:19279141

    Open questions at the time
    • Whether MRN recruits or activates TOPBP1 was still debated
    • Structural basis of ATRIP-TOPBP1 interface unresolved
  7. 2010 High

    Crystal structures of TOPBP1 N-terminal BRCT1-2-3 and C-terminal BRCT7-8 domains provided the first atomic-level understanding of how TOPBP1 reads phosphorylated partners: BRCT2 binds Rad9-pSer387 (CK2-phosphorylated), while BRCT7-8 undergoes dramatic conformational change to bind BACH1-pThr1133.

    Evidence X-ray crystallography with phosphopeptide co-crystals and binding assays

    PMID:20724438 PMID:21127055

    Open questions at the time
    • Structures of BRCT4-5 and BRCT6 not solved
    • Full-length TOPBP1 architecture unknown
  8. 2010 High

    TOPBP1's role in replication initiation was mechanistically defined: CDK2-dependent Treslin/TICRR binding to TOPBP1 mediates Cdc45 loading at replication origins, establishing TOPBP1 as the vertebrate Dpb11 functional ortholog in origin firing.

    Evidence Xenopus egg extract depletion/rescue, co-IP, chromatin fractionation, CDK-phosphorylation-dependent binding assays

    PMID:20116089 PMID:21700459

    Open questions at the time
    • Which BRCT domains bind Treslin not yet structurally resolved
    • How Chk1-mediated inhibition of Treslin-TOPBP1 binding is mechanistically achieved was unclear
  9. 2006 High

    Akt phosphorylation was shown to drive TOPBP1 oligomerization via BRCT7-8, functionally switching TOPBP1 from checkpoint activator to E2F1 transcriptional repressor, revealing a PI3K-Akt-TOPBP1 axis for apoptotic control.

    Evidence In vitro Akt kinase assays, size-exclusion chromatography, BRCT domain mutagenesis, apoptosis assays; later refined to identify Ser-1159 intramolecular binding to BRCT7-8

    PMID:17006541 PMID:24081328

    Open questions at the time
    • Whether oligomeric and monomeric TOPBP1 pools coexist in normal cells unclear
    • In vivo stoichiometry not measured
  10. 2013 High

    Genetic proof in mice demonstrated that the AAD is the essential ATR activation mechanism in vivo: W1147R knock-in is embryonic lethal, heterozygous MEFs show premature senescence and defective Chk1 signaling, and forced TOPBP1 dimerization restores ATR-Chk1 phosphorylation.

    Evidence Knock-in mouse model, conditional silencing, senescence and Chk1 phosphorylation assays, forced dimerization

    PMID:23950734

    Open questions at the time
    • Whether ETAA1 partially compensates in specific tissues not addressed
    • Mechanism by which dimerization promotes activation not structurally resolved
  11. 2014 Medium

    SIRT1-mediated deacetylation of TOPBP1 was identified as a switch that partitions TOPBP1 between replication origin suppression (deacetylated state favoring Treslin) and checkpoint activation (acetylated state favoring Rad9/ATR), adding a metabolic regulatory layer.

    Evidence Deacetylation assays, DNA fiber analysis of origin firing, Chk1 phosphorylation, siRNA of SIRT1

    PMID:25454945

    Open questions at the time
    • Acetylation sites on TOPBP1 not mapped
    • Whether acetylation directly alters BRCT domain conformation unclear
    • Independent confirmation needed
  12. 2018 High

    Systematic structural analysis of all major TOPBP1 BRCT domain pairs resolved their distinct phosphopeptide specificities—BRCT1-2 for Rad9, BRCT3-4 for Treslin, and additional motifs in RHNO1 and MDC1 homologs—providing a comprehensive structural code for TOPBP1 partner recognition.

    Evidence Multiple X-ray crystal structures, phosphopeptide binding assays, mutagenesis

    PMID:30295604

    Open questions at the time
    • BRCT5-6 structures and partner specificities incompletely characterized
    • Full-length architecture and domain–domain communication unknown
  13. 2019 High

    A mitosis-specific role for TOPBP1 was uncovered: CK2-phosphorylated MDC1 recruits TOPBP1 to DSBs exclusively in mitosis, where TOPBP1 forms filamentous structures that bridge broken chromosome ends until G1 repair, preventing micronuclei and chromosomal instability.

    Evidence Phosphopeptide binding, super-resolution microscopy of filaments, mutagenesis, genome stability assays

    PMID:30898438

    Open questions at the time
    • Molecular basis of filament assembly not structurally resolved
    • Whether TOPBP1 AAD activity contributes to mitotic tethering unclear
  14. 2021 High

    TOPBP1 phase separation was identified as the mechanism that amplifies ATR signaling: the intrinsically disordered AAD drives liquid-liquid phase separation into condensates, and single point mutations that disrupt condensation abolish ATR/Chk1 activation, directly coupling biophysical assembly to checkpoint output.

    Evidence In vitro purified-protein LLPS assays, optogenetic condensate induction, single-molecule imaging, mutagenesis

    PMID:33503405

    Open questions at the time
    • Whether condensates form at physiological TOPBP1 concentrations in vivo not confirmed
    • Relationship between condensates and filaments observed in mitosis unresolved
  15. 2022 High

    CIP2A was identified as a mitosis-specific partner that promotes TOPBP1 recruitment to DSBs upon nuclear envelope breakdown; the CIP2A-TOPBP1 axis is essential for preventing lethal mis-segregation in BRCA-deficient cells, establishing a therapeutic vulnerability.

    Evidence CRISPR synthetic lethality screens, co-IP, live-cell imaging, xenograft models

    PMID:35121901 PMID:35842428

    Open questions at the time
    • Whether CIP2A directly contacts TOPBP1 or acts through MDC1 intermediary not definitively resolved
    • Structural basis of CIP2A-TOPBP1 filament formation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure and domain–domain communication of TOPBP1, the relationship between phase-separated condensates and mitotic filaments, the mechanism by which dimerization/oligomerization differentially directs TOPBP1 toward checkpoint versus replication versus transcriptional functions, and whether TOPBP1 mutations contribute to human disease.
  • No full-length TOPBP1 structure available
  • Phase separation versus filament formation mechanistic relationship unresolved
  • No Mendelian disease association established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0005694 chromosome 3 GO:0005730 nucleolus 1
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-1640170 Cell Cycle 4 R-HSA-69306 DNA Replication 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-5357801 Programmed Cell Death 2
Partners
ATRATRIPBRIP1CIP2AMDC1RAD9ATICRRTP53BP1
Complex memberships
9-1-1-TOPBP1ATR-ATRIP-TOPBP1CIP2A-MDC1-TOPBP1

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 TopBP1 directly activates the ATR-ATRIP kinase complex through a conserved ATR-activating domain (AAD) located between BRCT domains VI and VII, distinct from its BRCT repeats. A single point mutation in the AAD abolishes ATR activation and checkpoint regulation in both Xenopus egg extracts and human cells. Recombinant protein assays, in vitro kinase assays, point mutagenesis, Xenopus egg extract functional complementation Cell High 16530042
2007 The 9-1-1 (Rad9-Hus1-Rad1) clamp activates ATR-Chk1 signaling primarily by recruiting TopBP1's ATR-activating domain to stalled replication forks; the BRCT I-II region of TopBP1 binds the phosphorylated C-terminal tail of Rad9 (pSer-373 in Xenopus), and this interaction is required for checkpoint-stimulated binding of TopBP1 to ATR-ATRIP. Co-immunoprecipitation in Xenopus egg extracts, phosphopeptide binding, point mutagenesis, checkpoint reconstitution assays The Journal of biological chemistry High 17575048 17636252
2007 Rad9 recruits TopBP1 to stalled forks via the TopBP1 ATR-activating domain (AD); fusion of the AD to PCNA or histone H2B bypasses the requirement for the 9-1-1 clamp, demonstrating that the primary role of 9-1-1 is to localize the ATR-activating domain. Domain fusion constructs, Chk1 phosphorylation assays, epistasis in human cells Genes & development High 17575048
2008 ATRIP contains a TopBP1-interacting region required for TopBP1-ATR association and TopBP1-mediated ATR activation; ATR itself contains a PIKK Regulatory Domain (PRD) required for activation by TopBP1 but not for basal kinase activity. Both are required for checkpoint signaling and cellular viability. Co-immunoprecipitation, in vitro kinase assays, domain mutagenesis, cellular complementation Genes & development High 18519640
2007 ATM phosphorylates TopBP1 on Ser-1131 (Xenopus), strongly enhancing association of TopBP1 with ATR-ATRIP; this phosphorylation is specifically required for ATR-dependent Chk1 phosphorylation in response to DSBs but not to replication stress. Phosphospecific antibodies, in vitro phosphorylation assays, Xenopus egg extract complementation with phosphorylation-site mutants The Journal of biological chemistry High 17446169
2010 Treslin (vertebrate Sld3 ortholog) associates with TopBP1 in a Cdk2-dependent manner prior to initiation of DNA replication; together they mediate CDK2-dependent loading of Cdc45 onto replication origins. Depletion of Treslin blocks chromosomal DNA replication. Xenopus egg extract depletion/rescue, co-immunoprecipitation, chromatin fractionation, siRNA in human cells Cell High 20116089
2011 CDK phosphorylation of conserved residues in Treslin/TICRR (human Sld3) generates binding sites for the BRCT repeats of TopBP1 (human Dpb11 ortholog), mediating the Treslin-TopBP1 interaction required for DNA replication. Under replication stress, Chk1 prevents this interaction to block late origin firing. Phosphopeptide binding assays, co-immunoprecipitation, mutagenesis, sequence analysis, Chk1 inhibition experiments Current biology : CB High 21700459
2010 MRN (MRE11-RAD50-NBS1) complex is required for recruitment of TOPBP1 to ATR-activating DNA structures containing ssDNA-dsDNA junctions; MRN-dependent TOPBP1 recruitment is necessary for CHK1 phosphorylation, while the 9-1-1 complex is required for TOPBP1 'activation' but not its recruitment. Xenopus egg extract depletion, defined ATR-activating DNA structures, CHK1 phosphorylation assays Molecular cell High 23582259
2009 The MRN complex (via NBS1) bridges ATM and TopBP1 together in Xenopus egg extracts; the interaction between NBS1's tandem BRCT repeats and TopBP1's first BRCT pair is required for ATM to phosphorylate and activate TopBP1, and for normal checkpoint response to DSBs. Co-immunoprecipitation in egg extracts, NBS1 depletion, BRCT domain mutants, checkpoint assays Molecular biology of the cell High 19279141
2001 Human TopBP1 is required for DNA replication, interacts with DNA polymerase epsilon, and colocalizes with BRCA1 at replication foci; upon replication stress, TopBP1 relocalizes with BRCA1 to replication forks. TopBP1 also interacts with checkpoint protein hRad9. Co-immunoprecipitation, confocal immunofluorescence, BrdU replication foci colocalization The Journal of biological chemistry Medium 11395493
2002 TopBP1 is phosphorylated in an ATM-dependent manner in response to DNA double-strand breaks; focus formation after DNA damage depends on BRCT5 domain of TopBP1, not on ATM-dependent phosphorylation. Downregulation of TopBP1 reduces cell survival via increased apoptosis. Phosphorylation assays, ATM-deficient cell lines, BRCT domain deletion mutants, morpholino knockdown Molecular and cellular biology Medium 11756551
2003 TopBP1 interacts with E2F1 specifically (not E2F2, E2F3, or E2F4) via the sixth BRCT domain of TopBP1 and the amino terminus of E2F1; this interaction is induced by DNA damage and ATM-mediated phosphorylation of E2F1, and through it TopBP1 represses E2F1 transcriptional activity, S-phase induction, and apoptosis. Co-immunoprecipitation, domain-mapping with deletion mutants, transcriptional reporter assays, immunofluorescence Molecular and cellular biology Medium 12697828
2004 TopBP1 recruits Brg1/Brm (SWI/SNF chromatin-remodeling complex) to E2F1-responsive promoters and represses E2F1 transcriptional activity and E2F1-dependent apoptosis through a pRb-independent, Brg1/Brm-dependent mechanism. Co-immunoprecipitation, chromatin immunoprecipitation, transcriptional reporter assays, RNAi, apoptosis assays Genes & development Medium 15075294
2006 Akt phosphorylates TopBP1 and induces its oligomerization through the seventh and eighth BRCT domains; this oligomerization is required for TopBP1 to interact with and repress E2F1 apoptotic activity, defining a PI3K-Akt-TopBP1 pathway for control of E2F1-dependent apoptosis. In vitro Akt kinase assays, co-immunoprecipitation, size exclusion chromatography, domain mutagenesis, apoptosis assays The EMBO journal High 17006541
2013 Akt-mediated phosphorylation of TopBP1 at Ser-1159 enables intramolecular binding of pS1159 to the 7th and 8th BRCT domains, driving TopBP1 oligomerization; this oligomerization switches TopBP1 function from checkpoint activation to transcriptional regulation by preventing TopBP1 chromatin recruitment and ATR binding under replicative stress. In vitro size exclusion chromatography, phosphopeptide binding assays, domain mutagenesis, Chk1 phosphorylation assays, Akt inhibitor experiments Molecular and cellular biology High 24081328
2011 TopBP1 mediates mutant p53 gain-of-function by: (1) interacting with p53 hot-spot mutants and NF-YA to promote mutant p53 and p300 recruitment to NF-Y target gene promoters; and (2) facilitating mutant p53 interaction with and inhibition of p63/p73 transcriptional activities. Co-immunoprecipitation, chromatin immunoprecipitation, reporter assays, siRNA depletion, xenograft models Molecular and cellular biology Medium 21930790
2009 TopBP1 interacts with and represses p53 via the seventh and eighth BRCT domains binding to the p53 DNA-binding domain, inhibiting p53 promoter binding activity. Co-immunoprecipitation, domain mutagenesis, chromatin immunoprecipitation, reporter assays Molecular and cellular biology Medium 19289498
2010 GEMC1 binds TopBP1 in Xenopus egg extracts; TopBP1 promotes GEMC1 loading onto chromatin during pre-RC formation. GEMC1 interacts with Cdc45 and Cdk2-CyclinE; CDK-phosphorylated GEMC1 stimulates replication initiation and is required for Cdc45 loading onto replication origins. Xenopus egg extract depletion/rescue, co-immunoprecipitation, chromatin fractionation, morpholino/siRNA in vertebrate cells Nature cell biology Medium 20383140
2010 TopBP1 is required for recruitment of both the 9-1-1 complex and DNA polymerase-alpha to stalled replication forks; DNA polymerase-alpha is also directly required for Rad9 loading, establishing an assembly pathway controlled by TopBP1. Xenopus egg extract depletion, chromatin fractionation, DNA damage site loading assays The Journal of cell biology Medium 19289795
2011 RHINO independently binds the 9-1-1 complex and TopBP1, is recruited to DNA damage sites by 9-1-1, and is required for Chk1 activation, functioning together with the 9-1-1 complex and TopBP1 to fully activate ATR. Co-immunoprecipitation, damage-induced focus formation, siRNA, Chk1 phosphorylation assays Science (New York, N.Y.) Medium 21659603
2006 TopBP1 depletion by RNAi strongly impairs phosphorylation of multiple ATR targets (Chk1, Nbs1, Smc1, H2AX) without interfering with ATR assembly at DNA damage sites; Claspin selectively regulates Chk1 phosphorylation downstream of TopBP1; TopBP1 is required for DNA damage-induced Claspin-Chk1 interaction. RNAi, immunofluorescence, co-immunoprecipitation, immunoblot of phosphorylation substrates Molecular and cellular biology Medium 16880517
2011 MDC1 interacts with TopBP1 via TopBP1's fifth BRCT domain and MDC1's SDT repeats; this interaction promotes TopBP1 accumulation at stalled replication forks via the H2AX/MDC1 cascade and is important for ATR-dependent Chk1 activation in response to replication stress. Co-immunoprecipitation, domain mapping, chromatin fractionation, Chk1 phosphorylation assays, siRNA The Journal of cell biology Medium 21482717
2019 MDC1 is phosphorylated by CK2 on a conserved surface recognized by TOPBP1, recruiting TOPBP1 to DSBs specifically in mitosis (not interphase); TOPBP1 forms filamentous structures that bridge MDC1 foci to tether DSBs until repair is reactivated in G1. Loss of MDC1-TOPBP1 interaction causes mitotic radiosensitivity, micronuclei, and chromosomal instability. Phosphopeptide binding, co-immunoprecipitation, super-resolution microscopy, mutagenesis, genome stability assays Molecular cell High 30898438
2022 CIP2A forms a mitosis-specific complex with MDC1 and TOPBP1; CIP2A is nuclear-excluded in interphase but gains chromatin access upon nuclear envelope breakdown and promotes TOPBP1 recruitment to mitotic DSBs. Loss of CIP2A causes radiosensitivity, micronuclei, and chromosomal instability. Co-immunoprecipitation, live-cell imaging, nuclear fractionation, siRNA/CRISPR, genome stability assays Nature communications High 35121901 35842428
2021 CIP2A-TOPBP1 complex in mitosis prevents lethal mis-segregation of acentric chromosomes in BRCA-deficient cells by tethering DSBs; CIP2A deficiency is synthetically lethal with BRCA1/2 mutations and physical disruption of the CIP2A-TOPBP1 complex is highly deleterious in BRCA-deficient tumors. Genome-scale CRISPR synthetic lethality screens, co-immunoprecipitation, chromosome segregation assays, xenograft models Nature cancer High 35121901
2021 TopBP1 self-assembles into micrometer-sized condensates (liquid-liquid phase separation in vitro); these condensates are the molecular switch that amplifies ATR kinase activity to phosphorylate Chk1 and slow replication forks. Single amino acid substitutions in the intrinsically disordered ATR-activation domain (AAD) disrupt both TopBP1 condensation and ATR/Chk1 signaling. Optogenetic condensate induction, purified protein LLPS assay, single-molecule imaging, ATR kinase assays, mutagenesis Molecular cell High 33503405
2010 Crystal structure of the N-terminal region of human TopBP1 reveals an unexpected triple-BRCT domain arrangement; the second BRCT domain provides a specific phosphopeptide-binding site that interacts with pSer387 of Rad9 (phosphorylated by CK2), while the third BRCT domain presents a distinct phospho-binding site. X-ray crystallography, phosphopeptide binding assays Nucleic acids research High 20724438
2010 Crystal structure of TopBP1 BRCT7/8 free and in complex with BACH1/FANCJ phosphopeptide (pThr1133) reveals a dramatic conformational change upon BACH1 binding, with BRCT domains pivoting to form a deep peptide-binding cleft; this provides the first structural mechanism for Thr(P) recognition among BRCT domains. X-ray crystallography, mutagenesis, phosphopeptide binding assays The Journal of biological chemistry High 21127055
2010 TopBP1 interacts with BACH1/FANCJ helicase via TopBP1's C-terminal tandem BRCT7/8 domains and S-phase-specific phosphorylation of BACH1 at Thr1133; this interaction is required for RPA loading onto chromatin and ATR-dependent phosphorylation events after replication stress. Co-immunoprecipitation, domain mapping, chromatin fractionation, phosphorylation assays, siRNA Molecular cell Medium 20159562
2015 TOPBP1 interacts with TOP2A via its C-terminal region and is required for TOP2A recruitment to ultra-fine anaphase bridges (UFBs) in mitosis; TOPBP1 recruitment to UFBs requires BRCT domain 5; TOPBP1 depletion leads to UFB accumulation mostly from centromeric loci. Co-immunoprecipitation, siRNA, mitotic UFB quantification by microscopy, domain mapping Nature communications Medium 25762097
2013 TopBP1 and RPA bind to ultrafine DNA bridges (UFBs) during anaphase; depletion of TopBP1/Dpb11 leads to accumulation of chromatin bridges and genome instability; TopBP1 prevents anaphase bridge accumulation via stimulation of ATR/Mec1 kinase and suppression of homologous recombination. Live-cell imaging, siRNA/depletion in DT40 and yeast, anaphase bridge quantification, epistasis The Journal of cell biology Medium 24379413
2016 TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin and homologous recombination; TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Co-immunoprecipitation, kinase assays, siRNA, RAD51 foci analysis, HR repair assays The Journal of cell biology Medium 26811421
2008 Miz1 is required for recruitment of a fraction of TopBP1 to chromatin and protects TopBP1 from proteasomal degradation by HectH9 (HUWE1) ubiquitin ligase; Myc antagonizes TopBP1-Miz1 binding, causing TopBP1 dissociation from chromatin, reduced TopBP1 levels, and attenuated ATR signaling. Co-immunoprecipitation, siRNA, proteasome inhibitor experiments, chromatin fractionation, ATR signaling assays The EMBO journal Medium 18923429
2003 PML associates with TopBP1 in vivo and at IR-induced foci; PML stabilizes TopBP1 protein post-translationally (not mRNA); in PML-deficient cells TopBP1 cannot form IR-induced foci and TopBP1 expression is reduced. Co-immunoprecipitation, immunofluorescence, pulse-chase labeling, siRNA, adenovirus-mediated PML overexpression Molecular and cellular biology Medium 12773567
2022 OTUD6A deubiquitinase interacts with TopBP1 at DNA damage sites, blocks interaction between TopBP1 and its E3 ubiquitin ligase UBR5, and decreases K48-linked polyubiquitination of TopBP1, thereby stabilizing TopBP1 and sustaining CHK1 S345 phosphorylation and replication stress checkpoint. Co-immunoprecipitation, ubiquitination assays, OTUD6A knockout, CHK1 phosphorylation assays, xenograft models Cell death and differentiation Medium 35768646
2014 SIRT1 deacetylates TopBP1; deacetylated TopBP1 suppresses replication origin firing, whereas acetylated TopBP1 preferentially interacts with Rad9 (9-1-1) and promotes ATR-Chk1 pathway activation. Loss of SIRT1 leads to increased origin firing and defective intra-S-phase checkpoint. Co-immunoprecipitation, deacetylation assays, replication origin firing (DNA fiber assay), Chk1 phosphorylation assays, siRNA Molecular cell Medium 25454945
2019 TOPBP1 and ETAA1 both contain ATR activation domains (AADs) requiring a conserved tryptophan residue and a predicted coiled-coil motif; the coiled-coil is required for ATR activation in vitro and in cells by mediating binding of the AADs to ATR. Bioinformatic analysis, in vitro kinase assays, co-immunoprecipitation, immunofluorescence of checkpoint signaling The Journal of biological chemistry Medium 30940728
2019 TOPBP1 BRCT domains 4-5 bind conserved phosphorylation sites in the N-terminus of 53BP1 in a phospho-dependent manner; this interaction is required for recruitment of TOPBP1, ATR, and CHK1 to 53BP1 damage foci and for the G1 DNA damage checkpoint, but not for 53BP1 or ATM foci formation. Phosphopeptide binding, co-immunoprecipitation, mutagenesis, immunofluorescence, cell cycle checkpoint assays eLife High 31135337
2010 53BP1 recruits TopBP1 to sites of DSBs specifically in G1 phase via BRCT domains 4-5; recruitment of TopBP1 to DSBs (but not to replication stress) depends on BRCT domains 1-2 and 4-5. TopBP1 contributes to the G1 cell cycle checkpoint. siRNA, domain-specific mutants, immunofluorescence, S-phase entry checkpoint assays The EMBO journal Medium 20871591
2016 TopBP1 directly binds RPA-coated single-stranded DNA via its BRCT2 domain; a point mutation abrogating this interaction prevents TopBP1 accumulation at DNA damage sites and blocks ATR activation. Protein binding assays, point mutagenesis, Xenopus egg extract chromatin loading assays, ATR activation assays The Journal of biological chemistry High 27129245
2015 TopBP1 forms foci in early mitosis at sites of unscheduled DNA synthesis and promotes SLX4 focus formation at these sites; TopBP1 depletion just before mitotic entry increases 53BP1 nuclear body formation in the subsequent G1, demonstrating that TopBP1 acts during mitosis to reduce transmission of DNA damage to daughter cells. Live-cell imaging, pulse-depletion (auxin-inducible degron), EdU incorporation, 53BP1 NB quantification, SLX4 colocalization The Journal of cell biology Medium 26283799
2020 Treacle recruits TOPBP1 to nucleoli via ATM/NBS1-dependent phosphorylation of conserved Ser/Thr residues at its C-terminus, which are bound by three BRCT domains of TOPBP1; TOPBP1 recruitment to the nucleolus is required for ATR-dependent inhibition of ribosomal RNA synthesis and nucleolar segregation in response to rDNA breaks. Co-immunoprecipitation, domain mapping, phosphopeptide binding, siRNA, rRNA synthesis assays, nucleolar morphology Nature communications Medium 31913317
2013 TopBP1 interacts with BLM helicase in a phosphorylation and cell-cycle-dependent manner (S-phase specific); TopBP1 prevents BLM ubiquitination by E3 ligase MIB1, stabilizing BLM in S phase; TopBP1 depletion decreases BLM protein levels and increases sister chromatid exchange. Co-immunoprecipitation, ubiquitination assays, siRNA, SCE assays, MIB1 knockout rescue Molecular cell Medium 24239288
2015 BLM-TopBP1 interaction requires BLM phosphorylation on Ser304 (not Ser338 as previously reported); disruption of BLM-TopBP1 interaction does not markedly affect BLM stability but increases sister chromatid exchanges, replication origin firing, and chromosomal aberrations, indicating a genome maintenance role independent of BLM stabilization. Co-immunoprecipitation with phospho-site mutants, BLM stability assays, SCE quantification, DNA fiber assay, chromosomal aberration analysis Molecular cell Medium 25794620
2017 TOPBP1 interacts with SMARCAD1 (human ortholog of yeast Fun30) in a CDK-phosphorylation-dependent manner at DSBs, promoting SMARCAD1 recruitment to damaged chromatin and facilitating efficient long-range DNA end resection. Co-immunoprecipitation, ChIP, resection assays (ssDNA quantification), cell-cycle mutants eLife Medium 28063255
2017 TOPBP1 is required for meiotic sex chromosome inactivation (MSCI) in mammalian male germ cells; conditional TOPBP1 deletion disrupts localization of silencing sensors (BRCA1) and effectors (ATR, γH2AFX) to the X chromosome, preventing X chromosome gene silencing and condensation via its ATR-activating function. Conditional knockout mice, immunofluorescence on meiotic spreads, RNA-seq Proceedings of the National Academy of Sciences of the United States of America Medium 29114052
2012 Conditional inactivation of TopBP1 in neural progenitors causes replication-associated DNA strand breaks leading to profound tissue ablation; the neurogenesis failure is substantially rescued by p53 inactivation but not ATM inactivation, placing TopBP1 upstream of p53 in a replication-coupled genome maintenance pathway. Conditional knockout mice (Emx1-Cre), immunohistochemistry, epistasis with p53-KO and ATM-KO Nature neuroscience Medium 22522401
2013 Knock-in of W1147R point mutation in the TopBP1 ATR-activation domain (AAD) is early embryonic lethal in mice; AAD inactivation in heterozygous MEFs impairs proliferation, promotes premature senescence, and compromises Chk1 signaling after UV irradiation. Enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation, supporting the model that TopBP1 AAD is the major ATR activator in metazoans. Knock-in mouse model, conditional silencing, senescence assays, Chk1 phosphorylation assays, forced dimerization PLoS genetics High 23950734
2022 CK2-phosphorylated HTATSF1 binds TOPBP1 to promote S-phase-specific TOPBP1 recruitment to DSBs via recognition of poly(ADP-ribosyl)ated RPA; the HTATSF1-TOPBP1 complex facilitates RPA-to-RAD51 exchange and homologous recombination. PARP inhibition blocks HTATSF1-TOPBP1 chromatin recruitment. Co-immunoprecipitation, PARylation assays, CK2 kinase assays, HR assays, PARP inhibitor experiments Molecular cell Medium 35597237
2018 Structural and biochemical characterization of multiple TOPBP1/Rad4 BRCT domain complexes reveals distinct specificities for phosphopeptide ligands; TOPBP1 BRCT1-2 binds phosphorylated RAD9, BRCT3-4 binds phosphorylated Treslin, and structurally-guided analysis identifies previously unknown phospho-dependent binding motifs in RHNO1 and MDC1 homologs. X-ray crystallography, phosphopeptide binding assays, mutagenesis, bioinformatic motif identification eLife High 30295604
2010 Rad17 loads 9-1-1 onto DNA in an ATP hydrolysis-dependent manner and then facilitates docking of 9-1-1 with TopBP1; ATP binding by Rad17 is required for 9-1-1-TopBP1 association, while ATP hydrolysis is required for 9-1-1 DNA loading and elevated TopBP1 chromatin accumulation. Xenopus egg extract assays, Rad17 ATPase mutants, 9-1-1 binding mutants, chromatin fractionation Molecular biology of the cell Medium 20110345
2009 TopBP1 binds damaged DNA preferentially via its C-terminus, and cooperates with damaged DNA to activate ATR in a length-dependent manner; TopBP1 binding to DNA is independent of DNA ends (circular and linear DNA stimulate equally). In vitro ATR kinase assay, DNA binding assays, comparison of circular vs linear DNA Nucleic acids research Medium 19139065
2011 Directly tethering TopBP1 to DNA via a lac repressor/operator system is sufficient to induce ATR-dependent Chk1 phosphorylation in vitro and in vivo; co-tethering Claspin with TopBP1 further synergizes Chk1 activation. Lac repressor tethering system in vitro and in mammalian cells, Chk1 phosphorylation assays The Journal of biological chemistry Medium 21502314
2010 CK2 phosphorylates Rad9 at Ser-341 and Ser-387; phosphorylation at Ser-387 is specifically required for interaction with TopBP1; in vitro CK2-phosphorylated 9-1-1 physically interacts with TopBP1, and Rad9 double phospho-deficient mutant causes UV and MMS hypersensitivity when overexpressed. In vitro CK2 kinase assay, phosphopeptide Co-IP, in vivo phospho-site mutagenesis, survival assays Genes to cells : devoted to molecular & cellular mechanisms Medium 20545769
2007 Human TopBP1 is required for G1/S progression by maintaining cyclin E/CDK2 activity and by loading replication components onto chromatin; these two roles are functionally separable as co-depletion of p21/p27 restores CDK2 activity but cells remain arrested due to defective chromatin loading of replication factors. siRNA, cell cycle analysis by FACS, CDK2 kinase assay, chromatin fractionation The Journal of biological chemistry Medium 17293600

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 TopBP1 activates the ATR-ATRIP complex. Cell 616 16530042
2007 The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes & development 385 17575048
2008 TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes & development 291 18519640
1995 Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint. Proceedings of the National Academy of Sciences of the United States of America 236 8524850
2007 The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. The Journal of biological chemistry 231 17636252
2010 Treslin collaborates with TopBP1 in triggering the initiation of DNA replication. Cell 206 20116089
2010 CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol (epsilon}, and GINS in budding yeast. Genes & development 201 20231317
2011 A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science (New York, N.Y.) 181 21659603
2001 BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. The Journal of biological chemistry 174 11395493
2002 A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. Molecular and cellular biology 151 11756551
2000 Dpb11 controls the association between DNA polymerases alpha and epsilon and the autonomously replicating sequence region of budding yeast. Molecular and cellular biology 144 10733584
2006 Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation. Molecular and cellular biology 141 16880517
2005 Identification and functional analysis of TopBP1 and its homologs. DNA repair 141 15897014
1998 Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Molecular and cellular biology 134 9742127
2010 BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Molecular cell 132 20159562
2004 TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Genes & development 126 15075294
2013 A role for the MRN complex in ATR activation via TOPBP1 recruitment. Molecular cell 123 23582259
2003 Regulation of E2F1 by BRCT domain-containing protein TopBP1. Molecular and cellular biology 122 12697828
2011 Regulation of DNA replication through Sld3-Dpb11 interaction is conserved from yeast to humans. Current biology : CB 115 21700459
2008 Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Molecular and cellular biology 106 18541674
2011 TopBP1 mediates mutant p53 gain of function through NF-Y and p63/p73. Molecular and cellular biology 104 21930790
2011 Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. The EMBO journal 104 21946560
2008 Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. The Journal of biological chemistry 102 18922789
2008 Dpb11 activates the Mec1-Ddc2 complex. Proceedings of the National Academy of Sciences of the United States of America 101 19028869
1999 DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 101 10097122
2019 MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis. Molecular cell 100 30898438
2014 TopBP1: A BRCT-scaffold protein functioning in multiple cellular pathways. DNA repair 100 25087188
2007 Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM. The Journal of biological chemistry 93 17446169
2010 GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication. Nature cell biology 91 20383140
2021 TopBP1 assembles nuclear condensates to switch on ATR signaling. Molecular cell 90 33503405
2002 A Functional interaction between the human papillomavirus 16 transcription/replication factor E2 and the DNA damage response protein TopBP1. The Journal of biological chemistry 90 11934899
2021 The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer. Nature cancer 88 35121901
2009 TopBP1 and DNA polymerase-alpha directly recruit the 9-1-1 complex to stalled DNA replication forks. The Journal of cell biology 88 19289795
2013 TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability. The Journal of cell biology 86 24379413
2006 Regulation of TopBP1 oligomerization by Akt/PKB for cell survival. The EMBO journal 86 17006541
2011 MDC1 collaborates with TopBP1 in DNA replication checkpoint control. The Journal of cell biology 85 21482717
2003 PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Molecular and cellular biology 85 12773567
2010 DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Molecular cell 83 20670896
2006 A CDK-catalysed regulatory phosphorylation for formation of the DNA replication complex Sld2-Dpb11. The EMBO journal 83 16619031
2015 TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells. The Journal of cell biology 82 26283799
2014 A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes & development 80 25030699
2009 A tale of two tails: activation of DNA damage checkpoint kinase Mec1/ATR by the 9-1-1 clamp and by Dpb11/TopBP1. DNA repair 80 19464966
2010 TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint. The EMBO journal 76 20871591
2015 TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution. Nature communications 70 25762097
2008 Miz1 and HectH9 regulate the stability of the checkpoint protein, TopBP1. The EMBO journal 70 18923429
2004 TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint. Molecular biology of the cell 70 14718568
2010 Adenovirus 12 E4orf6 inhibits ATR activation by promoting TOPBP1 degradation. Proceedings of the National Academy of Sciences of the United States of America 69 20566845
2002 Genetic and physical interactions between DPB11 and DDC1 in the yeast DNA damage response pathway. Genetics 69 11973288
2016 TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. The Journal of cell biology 67 26811421
2014 Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension. American journal of respiratory and critical care medicine 66 24702692
2015 Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication. Journal of virology 65 25694599
2010 Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1. Nucleic acids research 65 20724438
2008 How ATR turns on: TopBP1 goes on ATRIP with ATR. Genes & development 64 18519633
2019 Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Chemotherapy by Abrogating the TopBP1/ATR-Mediated DNA Damage Response. Clinical cancer research : an official journal of the American Association for Cancer Research 63 31533931
2020 Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation. Nature communications 62 31913317
2009 The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM. Molecular biology of the cell 61 19279141
2015 TopBP1 interacts with BLM to maintain genome stability but is dispensable for preventing BLM degradation. Molecular cell 58 25794620
2009 Regulation of p53 by TopBP1: a potential mechanism for p53 inactivation in cancer. Molecular and cellular biology 58 19289498
2010 Rad17 plays a central role in establishment of the interaction between TopBP1 and the Rad9-Hus1-Rad1 complex at stalled replication forks. Molecular biology of the cell 57 20110345
2010 TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells. The Journal of biological chemistry 57 21149450
2013 An essential function for the ATR-activation-domain (AAD) of TopBP1 in mouse development and cellular senescence. PLoS genetics 56 23950734
2009 TopBP1 and DNA polymerase alpha-mediated recruitment of the 9-1-1 complex to stalled replication forks: implications for a replication restart-based mechanism for ATR checkpoint activation. Cell cycle (Georgetown, Tex.) 54 19652550
2012 Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors. Nature neuroscience 53 22522401
2013 TopBP1 controls BLM protein level to maintain genome stability. Molecular cell 49 24239288
2014 A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint. Molecular cell 48 25454945
2010 Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control. The Journal of biological chemistry 48 21127055
2017 Targeting of the Fun30 nucleosome remodeller by the Dpb11 scaffold facilitates cell cycle-regulated DNA end resection. eLife 47 28063255
2022 The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis. Nature communications 46 35842428
2019 Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint. eLife 46 31135337
2004 Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor. Oncogene 45 15195143
1999 CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. Proceedings of the National Academy of Sciences of the United States of America 45 10500195
2009 Cooperative activation of the ATR checkpoint kinase by TopBP1 and damaged DNA. Nucleic acids research 44 19139065
2022 Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy. Cell death and differentiation 43 35768646
2017 TOPBP1Dpb11 plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1Rad9. The Journal of cell biology 43 28228534
2014 Targeting TopBP1 at a convergent point of multiple oncogenic pathways for cancer therapy. Nature communications 43 25400145
2014 TopBP1 and Claspin contribute to the radioresistance of lung cancer brain metastases. Molecular cancer 42 25216549
2012 S-phase sensing of DNA-protein crosslinks triggers TopBP1-independent ATR activation and p53-mediated cell death by formaldehyde. Cell cycle (Georgetown, Tex.) 42 22722496
2013 Efficient initiation of DNA replication in eukaryotes requires Dpb11/TopBP1-GINS interaction. Molecular and cellular biology 41 23629628
2016 Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage. The Journal of biological chemistry 39 27129245
2014 SIRT1 deacetylates TopBP1 and modulates intra-S-phase checkpoint and DNA replication origin firing. International journal of biological sciences 39 25516717
2021 CIP2A Interacts with TopBP1 and Drives Basal-Like Breast Cancer Tumorigenesis. Cancer research 38 34145035
2010 Casein kinase 2-dependent phosphorylation of human Rad9 mediates the interaction between human Rad9-Hus1-Rad1 complex and TopBP1. Genes to cells : devoted to molecular & cellular mechanisms 38 20545769
2017 DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line. Proceedings of the National Academy of Sciences of the United States of America 36 29114052
2007 TopBP1 associates with NBS1 and is involved in homologous recombination repair. Biochemical and biophysical research communications 36 17765870
2017 Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin. Proceedings of the National Academy of Sciences of the United States of America 35 28439015
2004 TopBP1 localises to centrosomes in mitosis and to chromosome cores in meiosis. Chromosoma 34 15138768
2022 A PARylation-phosphorylation cascade promotes TOPBP1 loading and RPA-RAD51 exchange in homologous recombination. Molecular cell 33 35597237
2020 Functions of TopBP1 in preserving genome integrity during mitosis. Seminars in cell & developmental biology 33 32912640
2019 Common motifs in ETAA1 and TOPBP1 required for ATR kinase activation. The Journal of biological chemistry 33 30940728
2010 Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination. DNA repair 33 21130053
2015 High levels of TopBP1 induce ATR-dependent shut-down of rRNA transcription and nucleolar segregation. Nucleic acids research 32 25916852
2014 Interaction between Rad9-Hus1-Rad1 and TopBP1 activates ATR-ATRIP and promotes TopBP1 recruitment to sites of UV-damage. DNA repair 32 25091155
2006 Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer. European journal of cancer (Oxford, England : 1990) 32 16930991
2018 BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands. eLife 31 30295604
2011 Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1). The Journal of biological chemistry 31 21502314
2011 The unstructured C-terminal tail of yeast Dpb11 (human TopBP1) protein is dispensable for DNA replication and the S phase checkpoint but required for the G2/M checkpoint. The Journal of biological chemistry 31 21956112
2010 Function of TopBP1 in genome stability. Sub-cellular biochemistry 31 20012580
2021 CK2 Phosphorylation of Human Papillomavirus 16 E2 on Serine 23 Promotes Interaction with TopBP1 and Is Critical for E2 Interaction with Mitotic Chromatin and the Viral Life Cycle. mBio 29 34544280
2007 Human TopBP1 participates in cyclin E/CDK2 activation and preinitiation complex assembly during G1/S transition. The Journal of biological chemistry 28 17293600
2013 Akt switches TopBP1 function from checkpoint activation to transcriptional regulation through phosphoserine binding-mediated oligomerization. Molecular and cellular biology 27 24081328