Affinage

RAD9A

Cell cycle checkpoint control protein RAD9A · UniProt Q99638

Length
391 aa
Mass
42.5 kDa
Annotated
2026-04-28
100 papers in source corpus 52 papers cited in narrative 50 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAD9A encodes a subunit of the heterotrimeric 9-1-1 (RAD9–RAD1–HUS1) sliding clamp, a PCNA-like toroidal ring that functions as a central platform for DNA damage checkpoint signaling and DNA repair. After DNA damage, the 9-1-1 complex is loaded onto RPA-coated single-stranded DNA by the RAD17-RFC clamp loader; CK2-mediated phosphorylation of the RAD9 C-terminal tail at Ser387 then recruits TopBP1 via its BRCT domains, triggering ATR→CHK1 checkpoint activation in a positive feedback loop (PMID:20545769, PMID:20724438, PMID:25091155, PMID:11799063). Beyond checkpoint signaling, the 9-1-1 complex directly stimulates multiple DNA repair enzymes—including FEN1, APE1, DNA ligase I, and NEIL1—thereby coordinating base excision repair and long-patch BER, while RAD9 also interacts with MLH1 to promote mismatch repair and antagonizes excessive DSB end-resection to regulate homologous recombination outcome (PMID:15556996, PMID:17426133, PMID:18842633, PMID:32576832). RAD9 additionally possesses a pro-apoptotic function: caspase-3 cleavage during apoptosis releases an N-terminal BH3-domain fragment that translocates to the cytosol and antagonizes BCL-xL, and RAD9 can directly transactivate p21 by binding p53-consensus sequences in its promoter (PMID:14508514, PMID:15184659).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1988 High

    The founding discovery that RAD9 controls the DNA damage checkpoint rather than repair itself established the concept of cell-cycle checkpoint genes, showing that rad9 mutants fail to arrest in G2 after irradiation yet retain repair capacity if artificially arrested.

    Evidence Genetic analysis of S. cerevisiae rad9 mutants with X-ray irradiation and microtubule poison arrest

    PMID:3291120

    Open questions at the time
    • Mechanism of damage sensing unknown
    • Signal transduction pathway from RAD9 to arrest not defined
    • Whether RAD9 also controls G1 arrest was untested
  2. 1993 High

    Extension of RAD9 checkpoint function to the G1/S transition demonstrated that RAD9 is a multi-phase checkpoint gene, not solely a G2 factor.

    Evidence Alpha-factor synchronization of S. cerevisiae rad9 mutants with UV/gamma irradiation

    PMID:8367452

    Open questions at the time
    • Biochemical mechanism of RAD9 signaling to G1 arrest unknown
    • Relationship to mammalian checkpoint unclear
  3. 1995 High

    Identification of single-stranded DNA at telomeres as a signal activating the RAD9 checkpoint provided the first molecular description of the upstream lesion sensed by RAD9.

    Evidence Genetic epistasis with cdc13 mutants plus DNA hybridization for ssDNA detection in S. cerevisiae

    PMID:7565765

    Open questions at the time
    • How RAD9 protein recognizes ssDNA-containing structures was unknown
    • Whether this applies to internal DSBs untested
  4. 1998 High

    Discovery that phosphorylated Rad9 directly binds the Rad53 FHA domain to activate checkpoint kinase signaling established Rad9 as a signal-transducing adaptor rather than a sensor per se.

    Evidence Co-immunoprecipitation and FHA domain mutagenesis with checkpoint assays in S. cerevisiae

    PMID:9657725

    Open questions at the time
    • Kinase responsible for Rad9 phosphorylation not identified
    • Stoichiometry and oligomeric state of the signaling complex unknown
  5. 1999 High

    Demonstration that the Rad9 BRCT domain mediates self-oligomerization dependent on phosphorylation revealed the structural basis for higher-order complex assembly required for checkpoint signal amplification.

    Evidence Two-hybrid, in vitro/in vivo co-IP, and BRCT point mutagenesis in S. cerevisiae

    PMID:10339432

    Open questions at the time
    • Oligomeric stoichiometry not determined
    • Whether BRCT-mediated oligomerization is conserved in human RAD9 unclear
  6. 2000 High

    Formation of the heterotrimeric RAD9–RAD1–HUS1 (9-1-1) complex as a PCNA-like ring was established across human and fission yeast systems, fundamentally redefining RAD9 as one subunit of a clamp rather than a standalone checkpoint protein.

    Evidence Co-immunoprecipitation, gel filtration, immunofluorescence, and computational fold prediction in S. pombe and human cells

    PMID:10648611 PMID:10852904

    Open questions at the time
    • No atomic-resolution structure yet
    • How the clamp is loaded onto DNA not determined
  7. 2000 High

    Discovery that human RAD9 interacts with BCL-2/BCL-xL and promotes apoptosis when overexpressed revealed an unexpected pro-apoptotic function separate from checkpoint signaling.

    Evidence Yeast two-hybrid, co-immunoprecipitation, and apoptosis assays with overexpression/antisense in mammalian cells

    PMID:10620799

    Open questions at the time
    • Mechanism of RAD9-mediated apoptosis (BH3 domain involvement) not yet identified
    • Physiological context unclear
  8. 2001 High

    Biochemical reconstitution showed that a Rad9-containing 560 kDa complex catalyzes Rad53 autophosphorylation in trans, establishing Rad9 as a scaffold that brings Rad53 molecules into proximity for reciprocal activation.

    Evidence Gel filtration, in vitro kinase assays with purified complexes from S. cerevisiae

    PMID:11511366

    Open questions at the time
    • The specific stoichiometry and composition of the 560 kDa complex beyond Rad9/Rad53 not fully defined
    • Whether Mec1 pre-phosphorylation of Rad53 is required for this step was debated
  9. 2001 High

    ATM was identified as the kinase directly phosphorylating human Rad9 at Ser272 after ionizing radiation, linking mammalian RAD9 to the ATM-dependent G1/S checkpoint.

    Evidence In vitro ATM kinase assay, in vivo phosphorylation in ATM-deficient cells, S272A mutagenesis with checkpoint assays

    PMID:11278446

    Open questions at the time
    • Whether other kinases phosphorylate Rad9 at additional sites unknown
    • Mechanistic link from pSer272 to G1/S arrest not fully elucidated
  10. 2002 High

    Demonstration that RAD17 loads the 9-1-1 complex onto chromatin after DNA damage, and that this enables ATR substrate recognition, defined the ordered loading mechanism for the checkpoint clamp.

    Evidence Chromatin fractionation, siRNA knockdown, and phosphorylation assays in human cells

    PMID:11799063

    Open questions at the time
    • Whether RAD17 forms a complete RFC-like pentamer was not resolved
    • ATP hydrolysis requirement for loading not tested
  11. 2002 High

    Mapping of Mec1/Tel1-phosphorylated [S/T]Q sites on Rad9 showed these are selectively required for Rad53 but not Chk1 activation, establishing that different phosphorylation events on Rad9 control distinct downstream kinase branches.

    Evidence Mass spectrometry, in vitro FHA domain binding, and mutagenesis in S. cerevisiae

    PMID:12049741

    Open questions at the time
    • The Chk1-activating domain of Rad9 not yet mapped
    • Structural basis for selectivity unknown
  12. 2003 High

    Identification of nine C-terminal tail phosphorylation sites in mammalian Rad9 required for Chk1 activation, and demonstration that PKCδ phosphorylation promotes 9-1-1 complex formation and apoptotic function, revealed the tail as a multi-kinase signaling hub.

    Evidence Mass spectrometry-based mapping in Mrad9−/− ES cells, PKCδ in vitro kinase assay, checkpoint/apoptosis assays

    PMID:12628935 PMID:12709442

    Open questions at the time
    • Which specific tail sites correspond to which kinases not fully resolved
    • How PKCδ phosphorylation promotes 9-1-1 assembly mechanistically unclear
  13. 2003 High

    Caspase-3 cleavage of RAD9 during apoptosis was shown to release an N-terminal BH3-domain fragment that translocates to the cytosol and antagonizes BCL-xL, providing a molecular mechanism for the pro-apoptotic role of RAD9.

    Evidence In vitro caspase cleavage, site-directed mutagenesis, caspase-3-deficient cells, immunofluorescence

    PMID:14508514

    Open questions at the time
    • Whether BH3 fragment is sufficient for apoptosis in vivo at endogenous levels not tested
    • Structural basis for BH3–BCL-xL interaction not determined
  14. 2004 High

    Multiple advances defined RAD9 as a multifunctional scaffold: the N-terminal Chk1-activation domain was mapped in yeast, Mec1 was shown to control Rad9 accumulation at DSBs by phosphorylating S/TQ motifs, and human RAD9 was found to directly transactivate p21 by binding p53-consensus sequences.

    Evidence Deletion mutagenesis and kinase assays in S. cerevisiae; ChIP at defined DSBs; EMSA and luciferase reporter assays in human cells

    PMID:14709724 PMID:15060150 PMID:15184659

    Open questions at the time
    • Whether RAD9 transcriptional activity is physiologically relevant at endogenous expression levels unclear
    • Full set of RAD9-regulated genes unknown
  15. 2004 High

    Mouse Rad9 knockout demonstrated embryonic lethality, extreme sensitivity to genotoxins, and genomic instability in ES cells, confirming that mammalian Rad9 is essential for genome integrity and viability.

    Evidence Targeted gene deletion in mouse, chromosome aberration analysis, clonogenic survival, G2 checkpoint assays

    PMID:15282322

    Open questions at the time
    • Tissue-specific requirements not yet explored
    • Which Rad9 functions (checkpoint vs. repair vs. apoptosis) cause lethality unknown
  16. 2004 High

    The 9-1-1 complex was shown to directly stimulate FEN1 on repair intermediates and the S. pombe Rad9 C-terminal phosphorylation was linked to TopBP1 (Rad4) recruitment for Chk1 activation, establishing the dual repair-enzyme-stimulating and checkpoint-adaptor roles of the clamp.

    Evidence In vitro FEN1 activity assays; co-IP of phospho-Rad9 mutants with Rad4/TopBP1 in S. pombe

    PMID:15155581 PMID:15556996

    Open questions at the time
    • Whether 9-1-1 stimulates FEN1 in vivo at repair sites not shown
    • Structural basis for FEN1–9-1-1 interaction unknown
  17. 2005 High

    Biochemical reconstitution demonstrated that Rad9 functions as a bona fide adaptor enabling Mec1 to phosphorylate Rad53, and the Tudor domain was identified as mediating Rad9 recruitment via methylated H3-K79, establishing chromatin-mark-dependent checkpoint activation.

    Evidence In vitro reconstitution with purified Mec1/Rad9/Rad53; Tudor domain binding to H3-K79me; ChIP and mutagenesis in S. cerevisiae

    PMID:16085488 PMID:16166626

    Open questions at the time
    • Whether Tudor–H3K79me interaction is the sole recruitment mechanism in all cell cycle phases unknown
    • Redundancy with γH2A binding not quantified
  18. 2005 High

    RAD9 C-terminal tail interaction with the RPA70 N-terminal OB fold was identified as a checkpoint recruitment domain (CRD) that directs 9-1-1 to damage sites independently of TopBP1 binding.

    Evidence Co-immunoprecipitation, siRNA knockdown of RPA, chromatin fractionation in human cells

    PMID:15897895

    Open questions at the time
    • Structural details of RAD9–RPA interface not resolved
    • Whether CRD and TopBP1-binding function cooperatively or sequentially unclear
  19. 2006 High

    The 9-1-1 complex was found to stimulate DNA ligase I and to localize to telomeres where it positively regulates telomerase, expanding its functional repertoire beyond DNA damage to telomere maintenance.

    Evidence In vitro ligation assays and co-IP of 9-1-1/ligase I; ChIP at telomeres, telomere length measurement in Hus1 KO cells

    PMID:16731526 PMID:16890531

    Open questions at the time
    • Whether 9-1-1 stimulates telomerase directly or through an intermediary unknown
    • Mechanism of telomere-specific 9-1-1 recruitment not identified
  20. 2007 High

    9-1-1 was shown to stimulate additional BER enzymes (NEIL1, APE1) and to interact with MLH1 for mismatch repair, establishing it as a general repair-enzyme-stimulating platform analogous to PCNA in replication.

    Evidence In vitro glycosylase/endonuclease activity assays, co-IP, reconstituted LP-BER, MMR assays with Rad9 point mutants

    PMID:17395641 PMID:17426133 PMID:18842633

    Open questions at the time
    • Whether 9-1-1 is loaded at repair sites by the same RAD17-RFC mechanism as at checkpoint sites not demonstrated
    • Relative contributions of individual subunits to each repair interaction not dissected
  21. 2008 High

    Structure-guided mutagenesis defined the RAD9 CRD–RPA70N interface and showed that Rad9 binding to H3-K79me via its Tudor domain inhibits DSB end-resection, revealing Rad9 as an anti-resection barrier analogous to 53BP1.

    Evidence NMR-validated RPA70N binding surface mutagenesis; quantitative ssDNA measurement (QAOS) and nuclease epistasis in S. cerevisiae

    PMID:18418382 PMID:18936170

    Open questions at the time
    • Direct physical mechanism of resection inhibition (steric block vs. recruitment of anti-resection factors) not resolved
    • Conservation of anti-resection function in mammalian RAD9A vs. 53BP1 not tested
  22. 2009 High

    Crystal structures of the human 9-1-1 ring at up to 2.5 Å resolution confirmed the PCNA-like toroidal architecture and revealed a single repair-enzyme-binding site competitively shared among repair factors and p21.

    Evidence X-ray crystallography from multiple groups, biochemical competition assays

    PMID:19446481 PMID:19464297 PMID:19535328

    Open questions at the time
    • Structure of the disordered RAD9 C-terminal tail (containing all major phosphorylation sites) not resolved
    • How 9-1-1 discriminates among repair substrates in vivo unclear
  23. 2010 High

    CK2 was identified as the kinase phosphorylating RAD9 Ser387, creating the TopBP1-binding site; structural analysis of TopBP1 BRCT domains confirmed specific recognition of phospho-Ser387; Rad17 ATP binding/hydrolysis was shown to be required for 9-1-1 loading and TopBP1 recruitment.

    Evidence In vitro CK2 kinase assays, TopBP1 BRCT crystal structure with phosphopeptide, Rad17 ATPase mutants in Xenopus extracts

    PMID:20110345 PMID:20545769 PMID:20724438

    Open questions at the time
    • Whether CK2 phosphorylation is constitutive or damage-regulated debated
    • Kinetic ordering of CK2 vs. ATR phosphorylation events on Rad9 tail unclear
  24. 2011 High

    A Dpb11–Mec1–Rad9 ternary complex was reconstituted in which CDK phosphorylation of Rad9 creates a Dpb11-binding site, restricting this checkpoint activation mode to S/G2 phases; separately, PRMT5-mediated arginine methylation of human Rad9 was shown to be required for CHK1 activation.

    Evidence In vitro reconstitution with purified yeast proteins; PRMT5 in vitro methylation assay and mutagenesis in human cells

    PMID:21321020 PMID:21946560

    Open questions at the time
    • Whether PRMT5 methylation affects Rad9 interactions with TopBP1 or RPA not tested
    • Interplay between CDK and CK2 phosphorylation in mammalian system unknown
  25. 2012 High

    The Slx4–Rtt107 complex was identified as a competitive antagonist of Rad9 at chromatin, dampening Rad53 hyperactivation during replication stress, and EM structure of the 9-1-1/FEN1/DNA ternary complex revealed distinct repair enzyme orientation compared to PCNA.

    Evidence Genetic suppressor epistasis and co-IP in S. cerevisiae; cryo-EM reconstruction of human 9-1-1/FEN1/DNA at 18 Å

    PMID:22586102 PMID:23160493

    Open questions at the time
    • Atomic-resolution structure of 9-1-1/FEN1 ternary complex not available
    • Whether Slx4 competition with Rad9 is conserved in mammals unknown
  26. 2013 High

    Germ-cell-specific Rad9a knockout in mice caused male infertility due to pachytene meiotic arrest with persistent autosomal DSBs, demonstrating an essential role for RAD9A in meiotic recombination and DSB repair.

    Evidence Conditional knockout mouse (Stra8-Cre), immunofluorescence for γH2AX/DMC1, spermatocyte staging

    PMID:23788429

    Open questions at the time
    • Whether the meiotic defect reflects checkpoint signaling, repair stimulation, or anti-resection function of Rad9 unknown
    • Female meiosis not examined
  27. 2018 High

    Sae2 was found to antagonize Rad9 accumulation at DSBs by competing for Tel1-mediated phosphorylation, revealing a phosphorylation-based competition mechanism that tunes the balance between checkpoint activation and resection.

    Evidence ChIP of Rad9 at DSBs, Tel1 phosphorylation competition assays, genetic epistasis in S. cerevisiae

    PMID:30510002

    Open questions at the time
    • Whether analogous competition occurs in mammalian cells (e.g., CtIP vs. 53BP1/RAD9) unknown
    • Quantitative phosphorylation dynamics not measured
  28. 2020 High

    Rad9 was shown to promote stable strand annealing during homologous recombination by antagonizing the anti-recombinogenic helicases Sgs1 and Mph1, revealing a post-checkpoint role in recombination outcome.

    Evidence Genetic analysis of recombination outcomes and helicase mutant epistasis in S. cerevisiae

    PMID:32576832

    Open questions at the time
    • Whether this anti-helicase function operates through direct protein interaction or chromatin-based mechanism unknown
    • Conservation in mammalian RAD9A not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of the disordered RAD9 C-terminal tail interactions with multiple partners; how 9-1-1 discriminates between checkpoint signaling and repair enzyme stimulation at damage sites; the relative physiological contributions of RAD9's checkpoint, repair, transcriptional, and apoptotic functions to tumor suppression; and whether RAD9A's anti-resection and recombination-promoting functions are conserved in mammals or have been assumed by 53BP1.
  • No structure of full-length Rad9 including C-terminal tail
  • In vivo separation-of-function alleles distinguishing checkpoint from repair roles in mammals lacking
  • Mechanism of RAD9 transcriptional activity at endogenous expression levels untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0042393 histone binding 3 GO:0003677 DNA binding 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005694 chromosome 5 GO:0005634 nucleus 3
Pathway
R-HSA-1640170 Cell Cycle 8 R-HSA-73894 DNA Repair 6 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1474165 Reproduction 1
Partners
BCL2L1FEN1HUS1MLH1RAD1RAD17RPA1TOPBP1
Complex memberships
9-1-1 (RAD9-RAD1-HUS1)RAD17-RFC clamp loader (functional partner)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The RAD9 gene product is essential for DNA damage-induced cell cycle arrest in G2 phase in S. cerevisiae; rad9 cells fail to arrest after irradiation and continue dividing until death, while repair can still occur if cells are artificially blocked in G2, indicating RAD9 controls the checkpoint rather than repair per se. Genetic analysis of rad9 mutants with X-ray irradiation, cell cycle analysis, microtubule poison arrest experiments Science High 3291120
1993 RAD9 is required for G1 cell cycle arrest after UV, 4NQO, or gamma radiation in S. cerevisiae, defining a second RAD9-dependent checkpoint at the G1/S transition in addition to the previously described G2 checkpoint. Genetic analysis of rad9 mutants with synchronization by alpha-factor, cell cycle progression assays after UV/gamma irradiation Proceedings of the National Academy of Sciences High 8367452
1995 Single-stranded DNA at telomeres (arising from Cdc13p failure) constitutes a specific signal activating the RAD9 checkpoint; cdc13 rad9 double mutants accumulate ssDNA at telomere-proximal sequences and divide at restrictive temperature, whereas cdc13 RAD9 cells arrest in G2. Genetic epistasis (cdc13 rad9 double mutants), DNA hybridization to detect ssDNA, analysis of mitotic recombination profile Molecular and Cellular Biology High 7565765
1998 Rad9 is phosphorylated in response to DNA damage in S. cerevisiae, and phosphorylated Rad9 interacts specifically with the C-terminal FHA domain of Rad53; inactivation of the FHA domain abolishes damage-dependent Rad53 phosphorylation and G2/M arrest. Co-immunoprecipitation, phosphorylation assays, FHA domain mutagenesis, cell cycle analysis Science High 9657725
1999 The BRCT domain of S. cerevisiae Rad9 mediates Rad9-Rad9 oligomerization (self-interaction), with the BRCT domain preferentially binding hyperphosphorylated Rad9; BRCT mutations abolish Rad9 hyperphosphorylation, Rad53 phosphorylation, and checkpoint function. Two-hybrid assay, in vitro and in vivo co-immunoprecipitation, point mutagenesis of BRCT motifs, UV survival and checkpoint assays Current Biology High 10339432
2000 Human RAD9 interacts with anti-apoptotic proteins BCL-2 and BCL-xL (but not BAX or BAD) via yeast two-hybrid and co-immunoprecipitation; overexpression of RAD9 induces apoptosis blocked by BCL-2 or BCL-xL, and antisense RAD9 suppresses MMS-induced cell death. Yeast two-hybrid, co-immunoprecipitation, overexpression and antisense knockdown in mammalian cells, apoptosis assays Nature Cell Biology High 10620799
2000 Human Rad9 (hRad9) is localized exclusively in the nucleus and becomes conversion to an extraction-resistant nuclear form after DNA damage; this damage-induced chromatin-associated form co-interacts with hHus1 and inducibly phosphorylated hRad1. Immunolocalization, biochemical fractionation, co-immunoprecipitation, response to multiple DNA-damaging agents Journal of Biological Chemistry High 10852904
2000 Rad9, Rad1, and Hus1 form a heterotrimeric PCNA-like ring (9-1-1 complex) in fission yeast (S. pombe); structure-based predictions confirmed by biochemical co-immunoprecipitation demonstrating Hus1-B in complex with Rad9 and Rad1; Rad17 controls nuclear localization of Hus1 but is in a distinct complex. Co-immunoprecipitation, gel filtration fractionation, indirect immunofluorescence, yeast two-hybrid, computational fold prediction validated biochemically Molecular and Cellular Biology High 10648611
2001 S. cerevisiae Rad9 forms two distinct large soluble complexes: a larger (≥850 kDa) hypophosphorylated complex in undamaged cells and a smaller (560 kDa) hyperphosphorylated complex with Rad53 after DNA damage. The 560 kDa complex catalyzes Rad53 autophosphorylation in trans, activating and releasing Rad53, requiring Rad53 kinase activity but not Mec1/Tel1 once the complex forms. Gel filtration, co-immunoprecipitation, in vitro kinase assays with purified complexes, genetic epistasis Molecular Cell High 11511366
2001 ATM directly phosphorylates human Rad9 at Ser272 in response to ionizing radiation in vitro and in vivo; this modification is delayed in ATM-deficient cells, and expression of hRad9 S272A disrupts IR-induced G1/S checkpoint activation and increases cellular IR sensitivity. In vitro kinase assay with ATM, in vivo phosphorylation by mass spectrometry/immunoblot, site-directed mutagenesis, checkpoint and survival assays in ATM-deficient cells Journal of Biological Chemistry High 11278446
2002 Human Rad17 recruits the Rad9 (9-1-1) complex onto chromatin after DNA damage; Rad17 binds chromatin prior to damage and is phosphorylated by ATR after damage; Rad17 phosphorylation is not required for Rad9 loading; the Rad1-Rad9-Hus1 complex recruited by Rad17 enables ATR to recognize its substrates. Chromatin fractionation, co-immunoprecipitation, siRNA knockdown, phosphorylation assays Genes & Development High 11799063
2002 Multiple Mec1/Tel1 consensus [S/T]Q sites within S. cerevisiae Rad9 are phosphorylated in response to DNA damage; these phosphorylation sites are selectively required for Rad53 (but not Chk1) checkpoint branch activation; phosphorylated Rad9 peptides bind Rad53 FHA domains in vitro. Mass spectrometry mapping of phosphorylation sites, site-directed mutagenesis, in vitro FHA domain binding assays, checkpoint activation assays Molecular Cell High 12049741
2002 The C-terminal region of human Rad9 contains a nuclear localization sequence (NLS) essential for nuclear import of the entire hRad9-hRad1-hHus1 complex; deletion of this NLS causes cytoplasmic accumulation of hRad1 and hHus1 and abrogates the G2 checkpoint. Deletion mutagenesis, subcellular fractionation, siRNA knockdown, fluorescence microscopy, checkpoint assays Journal of Biological Chemistry High 11994305
2003 Protein kinase Cδ (PKCδ) associates with and phosphorylates human Rad9 in vitro and in cells after DNA damage; PKCδ activation is necessary for 9-1-1 complex formation and for Rad9-Bcl-2 binding; inhibition of PKCδ attenuates Rad9-mediated apoptosis. Co-immunoprecipitation, in vitro kinase assay, PKCδ inhibition, 9-1-1 complex formation assays EMBO Journal High 12628935
2003 Phosphorylation of the Rad9 C-terminal tail is required for genotoxin-activated Chk1 activation; nine phosphorylation sites in the Rad9 tail (all in the C-terminal 119 aa) were identified; tail phosphorylation mutants abrogate HU- and UV-induced S-phase arrest and sensitize cells to UV and HU. Mass spectrometry-based phosphosite mapping, site-directed mutagenesis in Mrad9-/- ES cells, checkpoint assays, clonogenic survival Journal of Biological Chemistry High 12709442
2003 Caspase-3 cleaves human Rad9 at conserved sites during apoptosis; cleavage releases an N-terminal BH3-domain-containing fragment that translocates from the nucleus to the cytosol, binds BCL-xL, and promotes apoptosis; a cleavage-resistant Rad9 mutant protects cells from DNA damage-induced apoptosis. In vitro caspase cleavage assay, site-directed mutagenesis, caspase-3-deficient cell lines, immunofluorescence localization, apoptosis assays Oncogene High 14508514
2004 S. pombe Rad9 C-terminal T412/S423 phosphorylation by Rad3(ATR) (and Tel1(ATM) after damage) is required for association with the two-BRCT-domain region of Rad4(TOPBP1); this interaction activates the Chk1 damage checkpoint but not the Cds1 replication checkpoint. Co-immunoprecipitation of phosphorylation-site mutants, in vivo phosphorylation mapping, checkpoint activation assays Genes & Development High 15155581
2004 The human 9-1-1 complex (Rad9-Rad1-Hus1) directly binds and stimulates FEN1 (flap endonuclease 1) on flap, nick, and gapped DNA substrates simulating repair intermediates; stimulation partially requires 9-1-1 entry to double-stranded DNA ends but does not substitute for PCNA in DNA polymerase β stimulation. In vitro binding assay, in vitro FEN1 activity assays on defined DNA substrates, competition experiments PNAS High 15556996
2004 The N-terminus of S. cerevisiae Rad9 contains a Chk1 activation domain (CAD) specifically required for Chk1 phosphorylation/activation but not for Rad53 activation, demonstrating separable functional domains within Rad9 for the two checkpoint kinase branches. Deletion mutagenesis of Rad9 N-terminus, kinase activation assays for Chk1 and Rad53, genetic epistasis with cdc13-1 and yku70Δ Journal of Cell Science High 14709724
2004 Mec1 controls Rad9 accumulation at double-strand breaks (DSBs) in S. cerevisiae; Mec1 phosphorylates Rad9 S/TQ motifs in vitro, and multiple S/TQ mutations abolish Rad9 association with DSBs; Rad9-Rad53 interaction after DSB induction requires Mec1 kinase activity but Rad53 deletion does not affect Rad9-DSB association. ChIP (chromatin immunoprecipitation) at defined DSB, in vitro kinase assay with Mec1, S/TQ multi-site mutagenesis, co-immunoprecipitation Molecular and Cellular Biology High 15060150
2004 Human RAD9 activates transcription of p21 by binding to a p53-consensus DNA-binding sequence in the p21 promoter, as demonstrated by EMSA; overexpression of hRAD9 increases p21 RNA and protein and transactivates the p21 promoter in reporter assays. EMSA (electrophoretic mobility-shift assay), luciferase reporter assay, Northern blot, microarray PNAS High 15184659
2005 Dot1-dependent methylation of histone H3 Lys79 is required for Rad9 recruitment to DSBs and chromatin in S. cerevisiae; the Rad9 Tudor domain binds methylated H3-K79 in vitro and mediates focal accumulation at damage sites in vivo; loss of Dot1 or Tudor-domain mutation of Rad9 blocks Rad53 phosphorylation. Histone methyltransferase deletion epistasis, ChIP at DSBs, in vitro Tudor domain binding assay, Rad53 phosphorylation assay, Tudor domain point mutagenesis Molecular and Cellular Biology High 16166626
2005 Rad9 acts as a bona fide adaptor enabling direct phosphorylation of Rad53 by Mec1 in S. cerevisiae; biochemical reconstitution showed efficient Rad53 phosphorylation by Mec1 requires purified Rad9; this stimulatory activity depends on phospho/FHA-dependent Rad9-Rad53 interaction allowing Rad53 to be recognized as a Mec1 substrate. In vitro reconstitution with purified Mec1, Rad9, and Rad53; MS-based phosphosite mapping; phospho-FHA interaction assays Current Biology High 16085488
2005 Rad9 interacts with RPA70 and RPA32 subunits via an acidic peptide in the C-terminal RAD9 tail; this Rad9-RPA interaction promotes chromatin loading of the 9-1-1 complex and ATR signaling to CHK1; RPA knockdown blocks 9-1-1 chromatin association and 9-1-1 complex formation. Co-immunoprecipitation, siRNA knockdown of RPA, chromatin fractionation, immunofluorescence co-localization Oncogene High 15897895
2006 The human 9-1-1 complex stimulates DNA ligase I activity in a PCNA-independent manner; 9-1-1 improves DNA ligase I binding to nicked dsDNA; the 9-1-1/ligase I complex can be co-immunoprecipitated from human cells and this interaction is enhanced by UV irradiation. In vitro ligation assay on defined substrates, co-immunoprecipitation from human cells, DNA-binding assay Journal of Biological Chemistry High 16731526
2006 The mammalian 9-1-1 (Rad9/Rad1/Hus1) complex localizes to telomeres in human and mouse cells, associates with catalytically competent telomerase, and acts as a positive regulator of telomerase DNA polymerase activity; Hus1-deficient cells show severe telomere shortening. ChIP at telomeres, telomere length measurement (Q-FISH, Southern), co-immunoprecipitation of telomerase, Hus1 knockout mouse cells Current Biology High 16890531
2007 The Tudor domain of S. cerevisiae Rad9 is necessary for in vitro binding to H3-K79me and for Rad9 focal accumulation in vivo after DNA damage; Tudor domain function in checkpoint activation is restricted to G1 phase and its role in DNA repair is restricted to G2. In vitro histone binding assay with Tudor domain, in vivo focus formation by fluorescence microscopy, cell cycle-staged checkpoint assays, genetic epistasis with dot1Δ Yeast High 17243194
2007 Human NEIL1 DNA glycosylase interacts with all three 9-1-1 subunits (hRad9, hRad1, hHus1) individually and as a complex; the 9-1-1 complex significantly stimulates hNEIL1 glycosylase activity; hNEIL1 foci co-localize with hRad9 foci in H2O2-treated cells. Co-immunoprecipitation, GST pulldown, in vitro glycosylase activity assay, immunofluorescence co-localization Nucleic Acids Research High 17395641
2008 The basic cleft of RPA70 N-terminal OB-fold domain directly binds RAD9 via an acidic peptide in the RAD9 C-terminal tail (the checkpoint recruitment domain, CRD); mutation of the RAD9 CRD impairs localization to damage sites without disrupting 9-1-1 complex formation or TopBP1 binding; disruption impairs ATR→CHK1 signaling. In vitro binding assay, site-directed mutagenesis of RAD9 CRD, chromatin fractionation, ATR signaling assays, NMR-validated RPA70N binding surface Molecular and Cellular Biology High 18936170
2008 Dot1 histone methyltransferase and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres; Rad9 binding to methylated H3-K79 via its Tudor domain inhibits Rad50-dependent nuclease resection; loss of Rad9/Dot1 leads to faster ssDNA accumulation and faster Mec1 activation. Quantitative ssDNA measurement (QAOS), chromatin immunoprecipitation, genetic epistasis with nuclease mutants, CDK1 bypass assays EMBO Journal High 18418382
2008 TLK1B phosphorylates human Rad9 at S328; TLK1B interacts with Rad9 and promotes 9-1-1 complex assembly at DSBs; Rad9 and Asf1 compete for TLK1B binding; TLK1B promotes nucleosome reassembly adjacent to DSBs in a manner requiring interaction with Rad9. In vitro kinase assay, co-immunoprecipitation, chromatin immunoprecipitation at HO-induced DSB, site-directed mutagenesis (S328A), complementation in Rad9-null cells DNA Repair High 18940270
2009 Crystal structures of the human Rad9-Hus1-Rad1 (9-1-1) complex (at 3.2 Å and 2.5 Å) reveal a closed toroidal PCNA-like ring with notable structural differences among subunits in interdomain connecting loops; biochemical analysis identifies a single repair enzyme-binding site on 9-1-1 competitively blocked by p21; Rad9 C-terminal tail involvement in DNA binding is demonstrated. X-ray crystallography, biochemical binding competition assays, electrophoretic mobility-shift assay with DNA Molecular Cell / Journal of Molecular Biology / Journal of Biological Chemistry High 19446481 19464297 19535328
2010 CK2 phosphorylates Rad9 at Ser341 and Ser387 in the C-terminal tail; pSer387 mediates interaction with TopBP1 BRCT domains; phosphorylation of both sites is required for efficient TopBP1 interaction in vitro and for ATR-dependent checkpoint function; Rad9 S341A/S387A mutant causes hypersensitivity to UV and MMS. In vitro kinase assay with CK2, phosphomimetic/phospho-deficient mutagenesis, co-immunoprecipitation of TopBP1, cell survival assays Genes to Cells High 20545769
2010 Crystal structure of the N-terminal region of human TopBP1 reveals a triple-BRCT domain; the second BRCT domain specifically binds phosphorylated Ser387 of Rad9, and this phosphorylation is generated by CK2. X-ray crystallography of TopBP1 BRCT domains, phosphopeptide binding assays, CK2 kinase assay Nucleic Acids Research High 20724438
2010 Rad17 mediates the interaction of 9-1-1 with TopBP1 in Xenopus egg extracts; ATP binding to Rad17 is required for 9-1-1-TopBP1 association; ATP hydrolysis by Rad17 is required for 9-1-1 loading onto DNA; Rad17-dependent TopBP1 accumulation on chromatin requires both Rad17 and 9-1-1. Xenopus egg extract biochemistry, chromatin fractionation, Rad17 ATP-binding and hydrolysis mutants, dominant-negative 9-1-1 mutant unable to bind TopBP1 Molecular Biology of the Cell High 20110345
2010 S. pombe Rad9 is phosphorylated by DDK (Hsk1/Cdc7) in response to replication-induced DNA damage; DDK phosphorylation disrupts Rad9-RPA interaction; this requires prior Rad3(ATR) phosphorylation and 9-1-1 chromatin loading; DDK phosphorylation-deficient Rad9 mutants show abnormal DNA repair foci and decreased viability after replication stress. In vitro kinase assay, phosphosite mutagenesis, co-immunoprecipitation, DNA repair focus formation assay, cell viability assay Molecular Cell High 21095590
2011 Dpb11 forms a ternary complex with Mec1 and Rad9 required for efficient Rad9 phosphorylation in vitro and checkpoint activation in vivo; CDK phosphorylation of Rad9 on two key residues generates a Dpb11 BRCT-binding site, restricting this checkpoint signaling mechanism to post-G1 phases when CDK is active. In vitro phosphorylation reconstitution with purified Mec1/Dpb11/Rad9, CDK site mutagenesis, co-immunoprecipitation, checkpoint activation assays EMBO Journal High 21946560
2011 PRMT5 interacts with and methylates human Rad9 on arginine residues; arginine methylation of Rad9 is required for S/M and G2/M checkpoint activation and for CHK1 activation; a methylation-deficient Rad9 mutant shows impaired Chk1 phosphorylation. Co-immunoprecipitation, in vitro methylation assay, site-directed mutagenesis, checkpoint activation assays Nucleic Acids Research High 21321020
2012 Slx4-Rtt107 scaffold complex counteracts checkpoint adaptor Rad9 by competing with Rad9 for binding to Dpb11 and phosphorylated histone H2A, thereby dampening Rad53 hyperactivation at replication-induced lesions; deletion of Slx4/Rtt107 leads to Rad9-dependent Rad53 hyperactivation. Genetic epistasis (hypomorphic Rad53/H2A mutations rescue slx4/rtt107 sensitivity), co-immunoprecipitation, phosphorylation assays, checkpoint kinase activity assays Nature High 23160493
2013 RAD9A is expressed in male germ cells with peak in late pachytene/diplotene stages and is associated with the XY body; germ-cell-specific Rad9a deletion (Stra8-Cre) causes male infertility due to meiotic arrest in pachytene with increased unrepaired DSBs (γH2AX and DMC1 foci on autosomal chromosome axes). Conditional knockout mouse (Stra8-Cre), TUNEL assay, immunofluorescence for γH2AX/DMC1/TOPBP1, spermatocyte staging Journal of Cell Science High 23788429
2015 Yeast Rad9 (53BP1 ortholog) reduces Mre11 binding to a DSB; deletion of RAD9 leads to reduced Mre11 occupancy, Rad52 recruitment, efficient DSB end-tethering via Sgs1-dependent mechanism, and restored DSB repair in absence of Sae2 or with nuclease-deficient MRX. ChIP at defined DSB, genetic epistasis (rad9Δ suppresses sae2Δ repair defects), DSB end-tethering assays, live-cell imaging PLoS Genetics High 25569305
2018 Sae2 antagonizes Rad9 accumulation at DSBs by competing with other Tel1 substrates for Tel1-mediated phosphorylation, thereby reducing Rad9 binding to chromatin and to Rad53; this Sae2 function is independent of Mre11 nuclease activity. ChIP of Rad9 at DSBs, Tel1 phosphorylation competition assays, genetic epistasis with sae2Δ and mre11-nd mutants, co-immunoprecipitation PNAS High 30510002
2020 Yeast Rad9 promotes stable strand annealing between the recombinogenic filament and the donor template during homologous recombination by limiting strand rejection by Sgs1 and Mph1 helicases, thereby promoting long-tract gene conversion, crossover recombination, and break-induced replication after checkpoint activation. Genetic analysis of recombination outcomes, helicase mutant epistasis, physical recombination intermediate assays Nature Communications High 32576832
2008 Rad9 interacts with the mismatch repair protein MLH1 in both human and mouse cells; a single point mutation in Rad9 that disrupts this interaction significantly reduces MMR activity without affecting checkpoint functions, demonstrating a specific Rad9 role in MMR via MLH1 interaction. Co-immunoprecipitation, point mutagenesis of Rad9, MMR activity assays, checkpoint assays as controls Nucleic Acids Research High 18842633
2007 The 9-1-1 complex interacts with and stimulates APE1 (apurinic/apyrimidinic endonuclease 1) in vitro and in vivo; 9-1-1 preferentially stimulates APE1 and DNA polymerase β in reconstituted long-patch BER, revealing a hierarchy of 9-1-1 interactions with BER proteins. In vitro AP-endonuclease activity assay, co-immunoprecipitation, reconstituted LP-BER assay Nucleic Acids Research High 17426133
2009 Rad9 protein is highly mobile in undamaged cells but becomes immobilized at nuclear foci upon genotoxic stress; UV-induced Rad9 foci form predominantly in G1/S and IR-induced foci in S/G2; Rad9 focus formation requires processing of DNA lesions into ssDNA intermediates by NER (UV) or CtIP-mediated resection (IR). FRAP in living cells, immunofluorescence, siRNA knockdown of XPA/XPC and CtIP, cell cycle staging Cell Cycle High 19411845
2004 Deletion of mouse Rad9 (Mrad9) causes embryonic lethality at midgestation and embryonic fibroblast inviability; Mrad9-/- ES cells show increased spontaneous chromosomal aberrations, HPRT mutations, extreme sensitivity to UV/gamma/HU, and inability to maintain gamma-ray-induced G2 delay. Targeted gene deletion in mouse ES cells, chromosome aberration analysis, clonogenic survival assays, G2 checkpoint assays, complementation with human HRAD9 Molecular and Cellular Biology High 15282322
2006 Human Rad9 (hRad9) interacts with hHus1 and hRad1, forming the 9-1-1 complex; disruption of Rad1 causes destabilization of Rad9 and Hus1 and disintegration of the complex; Rad1 loss impairs ATR-dependent Chk1 but not ATM-dependent Chk2 activation. siRNA knockdown of Rad1, co-immunoprecipitation, checkpoint kinase activation assays, S-phase arrest assays Oncogene High 15184880
2014 9-1-1/TopBP1 interaction (mediated by CK2-phosphorylated Rad9 Ser387) activates ATR-ATRIP; TopBP1 and Rad9 can independently localize to UV damage sites; once co-recruited, 9-1-1/TopBP1 interaction induces ATR activation, which in turn promotes further TopBP1 accumulation in a positive feedback loop. Immunofluorescence at UV-damage sites, Rad9 phospho-deficient mutants, ATR inhibitor experiments, TopBP1/ATR co-localization assays DNA Repair High 25091155
2012 Human 9-1-1/FEN1/DNA ternary complex structure determined by single-particle EM at 18 Å reveals key differences from PCNA/FEN1/DNA in FEN1 orientation and interactions, consistent with 9-1-1 providing greater stability for DNA repair vs PCNA flexibility in replication. Cryo-EM single-particle reconstruction, molecular dynamics simulations, comparison with PCNA structure PNAS High 22586102

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science (New York, N.Y.) 1083 3291120
1995 Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Molecular and cellular biology 572 7565765
2002 Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes & development 421 11799063
1998 Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science (New York, N.Y.) 328 9657725
2004 Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA repair 256 15279787
2001 Budding yeast Rad9 is an ATP-dependent Rad53 activating machine. Molecular cell 248 11511366
2012 Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery. Nature cell biology 246 22484486
1993 Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 241 8514150
2005 Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Molecular and cellular biology 240 16166626
2000 Structure-based predictions of Rad1, Rad9, Hus1 and Rad17 participation in sliding clamp and clamp-loading complexes. Nucleic acids research 217 10871397
2000 Characterization of Schizosaccharomyces pombe Hus1: a PCNA-related protein that associates with Rad1 and Rad9. Molecular and cellular biology 202 10648611
2005 Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Current biology : CB 194 16085488
2002 Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Molecular cell 193 12049741
1993 RAD9-dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 183 8367452
1997 RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage. Genetics 169 9017389
2008 Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. The EMBO journal 162 18418382
1996 RAD9 and DNA polymerase epsilon form parallel sensory branches for transducing the DNA damage checkpoint signal in Saccharomyces cerevisiae. Genes & development 139 8895664
2008 The basic cleft of RPA70N binds multiple checkpoint proteins, including RAD9, to regulate ATR signaling. Molecular and cellular biology 137 18936170
2004 Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1. Genes & development 137 15155581
2003 Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9. The EMBO journal 131 12628935
2000 Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis. Nature cell biology 122 10620799
1998 The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage. Genetics 111 9725831
2004 Deletion of mouse rad9 causes abnormal cellular responses to DNA damage, genomic instability, and embryonic lethality. Molecular and cellular biology 107 15282322
1996 A human homolog of the Schizosaccharomyces pombe rad9+ checkpoint control gene. Proceedings of the National Academy of Sciences of the United States of America 106 8943031
2011 Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. The EMBO journal 104 21946560
2006 Histone H2A phosphorylation and H3 methylation are required for a novel Rad9 DSB repair function following checkpoint activation. DNA repair 104 16650810
1996 A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription. The EMBO journal 104 8670896
2009 Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation. Molecular cell 102 19446481
2001 ATM-dependent phosphorylation of human Rad9 is required for ionizing radiation-induced checkpoint activation. The Journal of biological chemistry 99 11278446
2007 Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain. Yeast (Chichester, England) 98 17243194
2003 Phosphorylation of human Rad9 is required for genotoxin-activated checkpoint signaling. The Journal of biological chemistry 98 12709442
2015 Functional interplay between the 53BP1-ortholog Rad9 and the Mre11 complex regulates resection, end-tethering and repair of a double-strand break. PLoS genetics 93 25569305
2005 Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells. Oncogene 93 15897895
2000 Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage. The Journal of biological chemistry 93 10852904
2004 The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1. Proceedings of the National Academy of Sciences of the United States of America 88 15556996
1991 Cloning and characterisation of the rad9 DNA repair gene from Schizosaccharomyces pombe. Nucleic acids research 86 1852603
1998 Hydrogen peroxide causes RAD9-dependent cell cycle arrest in G2 in Saccharomyces cerevisiae whereas menadione causes G1 arrest independent of RAD9 function. The Journal of biological chemistry 84 9535829
2012 DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9. Nature 82 23160493
2006 Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1. The Biochemical journal 81 16879101
1977 Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6 and rad9 of Saccharomyces cerevisiae. Mutation research 81 335235
1999 The BRCT domain of the S. cerevisiae checkpoint protein Rad9 mediates a Rad9-Rad9 interaction after DNA damage. Current biology : CB 78 10339432
2009 Structure and functional implications of the human rad9-hus1-rad1 cell cycle checkpoint complex. The Journal of biological chemistry 71 19535328
2004 Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe. The Journal of biological chemistry 70 15533944
2011 A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage. Nucleic acids research 66 21321020
2002 Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event. The Journal of biological chemistry 66 12228248
1998 The Saccharomyces cerevisiae RAD9 checkpoint reduces the DNA damage-associated stimulation of directed translocations. Molecular and cellular biology 66 9488434
2010 Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1. Nucleic acids research 65 20724438
2007 The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. Nucleic acids research 65 17395641
2009 Crystal structure of the human rad9-hus1-rad1 clamp. Journal of molecular biology 63 19464297
2008 Tousled homolog, TLK1, binds and phosphorylates Rad9; TLK1 acts as a molecular chaperone in DNA repair. DNA repair 63 18940270
2007 The checkpoint clamp, Rad9-Rad1-Hus1 complex, preferentially stimulates the activity of apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta in long patch base excision repair. Nucleic acids research 61 17426133
2004 Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Oncogene 59 15184880
2000 HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins. The Journal of biological chemistry 59 10846170
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
2015 Escape of Sgs1 from Rad9 inhibition reduces the requirement for Sae2 and functional MRX in DNA end resection. EMBO reports 54 25637499
2010 A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions. Journal of molecular biology 54 20816984
2003 Role of the Saccharomyces cerevisiae Rad9 protein in sensing and responding to DNA damage. Biochemical Society transactions 54 12546694
1989 Control of G2 delay by the rad9 gene of Saccharomyces cerevisiae. Journal of cell science. Supplement 54 2699734
2006 Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity. Journal of cellular biochemistry 53 16365875
2004 A domain of Rad9 specifically required for activation of Chk1 in budding yeast. Journal of cell science 53 14709724
2002 A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex. The Journal of biological chemistry 52 11994305
2018 Mrc1 and Rad9 cooperate to regulate initiation and elongation of DNA replication in response to DNA damage. The EMBO journal 50 30158111
2012 Repair complexes of FEN1 endonuclease, DNA, and Rad9-Hus1-Rad1 are distinguished from their PCNA counterparts by functionally important stability. Proceedings of the National Academy of Sciences of the United States of America 48 22586102
2009 The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair by sister chromatid recombination in Saccharomyces cerevisiae. Genetics 46 19332880
2006 Mechanism of stimulation of human DNA ligase I by the Rad9-rad1-Hus1 checkpoint complex. The Journal of biological chemistry 45 16731526
2006 Telomere and telomerase modulation by the mammalian Rad9/Rad1/Hus1 DNA-damage-checkpoint complex. Current biology : CB 44 16890531
2004 Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism. Molecular and cellular biology 44 15060150
2004 Human RAD9 checkpoint control/proapoptotic protein can activate transcription of p21. Proceedings of the National Academy of Sciences of the United States of America 44 15184659
2017 TOPBP1Dpb11 plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1Rad9. The Journal of cell biology 43 28228534
2018 Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection. Proceedings of the National Academy of Sciences of the United States of America 42 30510002
2015 SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp. BMC molecular biology 41 26063178
2008 Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1. Nucleic acids research 40 18842633
2001 Structure-function analysis of fission yeast Hus1-Rad1-Rad9 checkpoint complex. Molecular biology of the cell 40 11739777
2000 Schizosaccharomyces pombe Rad9 contains a BH3-like region and interacts with the anti-apoptotic protein Bcl-2. FEBS letters 40 10996309
2009 TLK1B promotes repair of DSBs via its interaction with Rad9 and Asf1. BMC molecular biology 39 20021694
2011 The role of RAD9 in tumorigenesis. Journal of molecular cell biology 38 21278450
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
2010 Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS genetics 37 20808892
2012 Rad9 protein contributes to prostate tumor progression by promoting cell migration and anoikis resistance. The Journal of biological chemistry 35 23066031
2004 Rad9 protects cells from topoisomerase poison-induced cell death. The Journal of biological chemistry 35 14988409
2021 DNMT1 and DNMT3B regulate tumorigenicity of human prostate cancer cells by controlling RAD9 expression through targeted methylation. Carcinogenesis 34 32780107
2017 p53 and RAD9, the DNA Damage Response, and Regulation of Transcription Networks. Radiation research 34 28140789
2010 DDK phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin. Molecular cell 33 21095590
2014 Interaction between Rad9-Hus1-Rad1 and TopBP1 activates ATR-ATRIP and promotes TopBP1 recruitment to sites of UV-damage. DNA repair 32 25091155
2008 ATR and Rad17 collaborate in modulating Rad9 localisation at sites of DNA damage. Journal of cell science 32 19020305
2008 Identification of androgen-selective androgen-response elements in the human aquaporin-5 and Rad9 genes. The Biochemical journal 31 18215141
2012 Contributions of Rad9 to tumorigenesis. Journal of cellular biochemistry 30 22034047
2006 Phosphorylation of Xenopus Rad1 and Hus1 defines a readout for ATR activation that is independent of Claspin and the Rad9 carboxy terminus. Molecular biology of the cell 30 16436514
2005 Human Rad9 is required for the activation of S-phase checkpoint and the maintenance of chromosomal stability. Genes to cells : devoted to molecular & cellular mechanisms 30 15773892
2003 Caspase-3-mediated cleavage of Rad9 during apoptosis. Oncogene 30 14508514
1996 Cdc20, a beta-transducin homologue, links RAD9-mediated G2/M checkpoint control to mitosis in Saccharomyces cerevisiae. Molecular & general genetics : MGG 29 9003297
2013 The DNA damage checkpoint protein RAD9A is essential for male meiosis in the mouse. Journal of cell science 28 23788429
2008 Targeted deletion of Rad9 in mouse skin keratinocytes enhances genotoxin-induced tumor development. Cancer research 28 18632607
2007 Jab1 mediates protein degradation of the Rad9-Rad1-Hus1 checkpoint complex. Journal of molecular biology 27 17583730
2020 Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases. Nature communications 26 32576832
2019 Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9. PloS one 26 31310624
2016 Functional compartmentalization of Rad9 and Hus1 reveals diverse assembly of the 9-1-1 complex components during the DNA damage response in Leishmania. Molecular microbiology 26 27301589
2009 Cell cycle-dependent processing of DNA lesions controls localization of Rad9 to sites of genotoxic stress. Cell cycle (Georgetown, Tex.) 26 19411845
2009 Repair activities of human 8-oxoguanine DNA glycosylase are stimulated by the interaction with human checkpoint sensor Rad9-Rad1-Hus1 complex. DNA repair 26 19615952
2011 The RAD9-RAD1-HUS1 (9.1.1) complex interacts with WRN and is crucial to regulate its response to replication fork stalling. Oncogene 25 22002307