Affinage

RAD9A

Cell cycle checkpoint control protein RAD9A · UniProt Q99638

Length
391 aa
Mass
42.5 kDa
Annotated
2026-06-10
100 papers in source corpus 66 papers cited in narrative 65 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAD9A encodes the RAD9 subunit of the heterotrimeric 9-1-1 (RAD9-HUS1-RAD1) DNA-damage clamp and is a core sensor/transducer of the DNA damage checkpoint, originally defined in budding yeast as essential for cell-cycle arrest in G1, S, and G2 after genotoxic insult (PMID:3291120, PMID:8367452, PMID:9017389). RAD9, RAD1, and HUS1 assemble into a toroidal heterotrimeric ring structurally indistinguishable from the PCNA sliding clamp (PMID:12167163, PMID:19446481, PMID:19464297), which is recruited onto RPA-coated damage sites by the RAD17-RFC clamp loader (PMID:11799063, PMID:15897895). Once loaded on chromatin—a proximal, kinase-independent event (PMID:12228248)—the clamp localizes the ATR-activating domain of TopBP1 through direct binding of CK2-phosphorylated RAD9 C-terminal residues (Ser-341/Ser-387, and Ser-373 in Xenopus), driving ATR-dependent CHK1 activation and S/G2 checkpoint arrest (PMID:17575048, PMID:17636252, PMID:20724438, PMID:20545769). In yeast the orthologous Rad9 acts as a phospho-dependent signaling adaptor that, after Mec1/Tel1 phosphorylation at S/TQ motifs, engages the Rad53 FHA domain to enable Rad53 activation (PMID:9755168, PMID:9657725, PMID:11124038, PMID:12049741, PMID:16085488); its chromatin recruitment is governed by the Tudor domain binding Dot1-methylated H3K79 and the BRCT domains recognizing phospho-H2A/oligomerizing RAD9 (PMID:10339432, PMID:16166626, PMID:17721446, PMID:17243194). Beyond checkpoint signaling, the 9-1-1 clamp directly stimulates multiple base-excision-repair enzymes including FEN1, Pol β, APE1, NEIL1, and TDG (PMID:15314187, PMID:15556996, PMID:17395641, PMID:17855402, PMID:17426133), and RAD9 contributes to homologous recombination, telomere maintenance, and mismatch repair through interactions with RAD51, telomerase, and MLH1 (PMID:16479004, PMID:16890531, PMID:18842633). RAD9 also has a pro-apoptotic function: it binds and antagonizes BCL-2/BCL-xL, and caspase-3 cleavage releases a BH3-containing N-terminal fragment that translocates to the cytosol to promote apoptosis (PMID:10620799, PMID:14508514). Genetic deletion of mouse Rad9 causes midgestation embryonic lethality, genomic instability, and hypersensitivity to genotoxins, establishing its essential role in genome maintenance (PMID:15282322).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1988 High

    Established that RAD9 is required for cell-cycle arrest after DNA damage, defining the existence of a damage checkpoint dependent on a dedicated gene rather than the repair machinery itself.

    Evidence Genetic analysis of rad9 mutants with X-irradiation and cell cycle analysis in S. cerevisiae

    PMID:3291120

    Open questions at the time
    • No molecular function or biochemical activity assigned
    • Checkpoint mechanism downstream of RAD9 unknown
  2. 1993 High

    Extended RAD9 checkpoint function to G1/S and S-phase and placed it genetically with RAD17/RAD24 upstream of MEC1/RAD53, mapping its position in the checkpoint hierarchy.

    Evidence Genetic epistasis, cell-cycle synchronization, and double-mutant analysis across radiation conditions in yeast

    PMID:8367452 PMID:8514150 PMID:9017389 PMID:9564050

    Open questions at the time
    • Biochemical nature of the signal transduced unknown
    • Did not establish whether RAD9 acts as enzyme, adaptor, or structural component
  3. 1996 High

    Showed RAD9 controls a damage-induced transcriptional regulon and defines a sensory branch parallel to Pol epsilon, broadening its role beyond simple cell-cycle arrest.

    Evidence Northern blots, lacZ reporters, and genetic epistasis with Rad53 phosphorylation readouts in yeast deletion mutants

    PMID:8670896 PMID:8895664

    Open questions at the time
    • Mechanism linking RAD9 to transcription not resolved
    • Direct vs indirect transcriptional role unclear
  4. 1998 High

    Identified RAD9 as a phospho-dependent adaptor: damage-induced Mec1/Tel1 hyperphosphorylation of Rad9 creates an FHA-domain docking site for Rad53, defining the molecular link between sensor and effector kinase.

    Evidence Phosphatase treatment, co-IP, FHA domain mutagenesis, and checkpoint functional assays in yeast

    PMID:9564050 PMID:9657725 PMID:9755168

    Open questions at the time
    • Specific phosphosites not yet mapped
    • Structural basis of FHA recognition not yet defined
  5. 1999 High

    Demonstrated that human RAD9, RAD1, and HUS1 form a damage-responsive heterotrimeric complex and that the Rad9 BRCT domain mediates phospho-dependent oligomerization required for checkpoint function.

    Evidence Co-IP of human proteins, two-hybrid, BRCT point mutagenesis, and checkpoint survival assays

    PMID:10339432 PMID:9872989

    Open questions at the time
    • Architecture of the complex unknown
    • Whether complex resembled a clamp not yet shown
  6. 2000 High

    Predicted and began testing that 9-1-1 is a PCNA-like sliding clamp loaded by an RFC-like RAD17, reframing RAD9 as a structural DNA-binding clamp subunit; concurrently linked human RAD9 to apoptosis via BCL-2/BCL-xL.

    Evidence Computational fold recognition, fission-yeast complex co-IP/localization, NMR of Rad53 FHA1 with Rad9 phosphopeptide, and two-hybrid/co-IP with apoptosis assays

    PMID:10620799 PMID:10648611 PMID:10871397 PMID:11124038

    Open questions at the time
    • Clamp model still computational/inferred at this stage
    • Mechanism of apoptotic function not yet defined
  7. 2001 High

    Reconstituted Rad9 as a scaffold catalyzing Rad53 activation in trans and confirmed PCNA-like structure-function features, distinguishing damage-specific from undamaged Rad9 complexes.

    Evidence Gel filtration, co-IP, in vitro kinase reconstitution, and structure-function mutagenesis in budding and fission yeast

    PMID:11511366 PMID:11739777

    Open questions at the time
    • Reconciliation of scaffold vs adaptor models not yet settled
    • Loading mechanism onto DNA not directly visualized
  8. 2002 High

    Defined chromatin loading as a proximal, kinase-independent event mediated by RAD17 recruitment of 9-1-1, mapped Mec1/Tel1 SQ phosphosites selectively required for the Rad53 branch, and directly visualized the 9-1-1 ring by EM as PCNA-like.

    Evidence Chromatin fractionation with PIKK inhibitors, SQ-site mutagenesis with FHA pulldowns, and EM of baculovirus-reconstituted human 9-1-1 and Rad17-RFC

    PMID:11799063 PMID:12049741 PMID:12167163 PMID:12228248

    Open questions at the time
    • How RPA directs loading not yet established
    • Atomic structure of clamp not yet available
  9. 2002 High

    Connected RAD9 to apoptotic signaling kinases, showing c-Abl phosphorylates Rad9 Tyr-28 in its BH3 domain to promote BCL-xL binding, linking the checkpoint protein to genotoxic cell-death decisions.

    Evidence Co-IP, in vitro kinase assays, Tyr-28 mutagenesis, and apoptosis assays in mammalian cells

    PMID:11971963

    Open questions at the time
    • Quantitative contribution of apoptotic vs checkpoint role unclear
    • Single-lab phosphosite assignment
  10. 2003 High

    Identified PKCδ as a regulator of 9-1-1 assembly and Rad9-BCL-2 binding, and showed caspase-3 cleavage liberates a pro-apoptotic BH3 N-terminal fragment, establishing post-translational control of RAD9's life/death function.

    Evidence Co-IP, in vitro kinase and caspase cleavage assays, cleavage-resistant mutants, and apoptosis assays in caspase-3-deficient cells

    PMID:12628935 PMID:14508514

    Open questions at the time
    • Physiological balance between cleaved and intact RAD9 pools unquantified
    • In vivo significance of apoptotic fragment not tested in animals
  11. 2003 High

    Demonstrated that RAD9 C-terminal tail phosphorylation drives CHK1 activation and replication-stress survival, separating the CHK1 branch determinants in the mammalian protein.

    Evidence Systematic phosphosite mutagenesis with complementation of Mrad9-/- ES cells and checkpoint assays across UV/IR/HU

    PMID:12709442

    Open questions at the time
    • Identity of the kinase(s) phosphorylating the tail not yet defined
    • Downstream effector recruited by phospho-tail unknown
  12. 2004 High

    Established that the 9-1-1 clamp directly stimulates base-excision-repair enzymes (Pol β, FEN1), revealing a repair-promoting scaffold function distinct from PCNA and from checkpoint signaling.

    Evidence In vitro pulldowns and polymerase/nuclease activity assays with specificity controls across multiple polymerases

    PMID:15184659 PMID:15314187 PMID:15556996

    Open questions at the time
    • Whether BER stimulation occurs in vivo at lesions not directly shown
    • Coordination with checkpoint loading unclear
  13. 2004 High

    Genetically separated the Rad53 and Chk1 activation functions of yeast Rad9 into distinct domains, mapped Mec1-driven Rad9 accumulation at DSBs by ChIP, and showed mouse Rad9 is essential for embryonic viability and genome stability.

    Evidence Domain deletion with kinase readouts, ChIP with SQ mutagenesis, and targeted Mrad9 deletion with survival/mutation/complementation assays

    PMID:14709724 PMID:14988409 PMID:15060150 PMID:15282322

    Open questions at the time
    • Mechanism distinguishing Chk1 vs Rad53 branch recruitment incomplete
    • Cause of embryonic lethality not resolved to a single pathway
  14. 2005 High

    Defined the chromatin-recruitment code for Rad9 via Dot1-methylated H3K79 binding by the Tudor domain and RPA interaction in human cells, and clarified the adaptor mechanism enabling Mec1 to phosphorylate Rad53.

    Evidence Checkpoint assays in dot1Δ/H3K79 mutants with Tudor mutagenesis, biochemical reconstitution with mass-spec phosphomapping, and co-IP/siRNA/chromatin fractionation for RPA

    PMID:15897895 PMID:16085488 PMID:16166626

    Open questions at the time
    • Relative contributions of histone marks vs RPA to recruitment not fully partitioned
    • Human RPA-binding interface not yet mapped at residue level
  15. 2006 Medium

    Extended RAD9/9-1-1 function to homologous recombination, telomere maintenance, and additional BER glycosylase stimulation, broadening the clamp's genome-maintenance roles.

    Evidence Co-IP with Rad51 and telomerase, HR and telomere FISH assays, and in vitro NEIL1 glycosylase stimulation with co-localization

    PMID:16479004 PMID:16890531 PMID:17395641

    Open questions at the time
    • Direct vs indirect role in HR/telomere not fully dissected
    • Single-lab functional assignments
  16. 2007 High

    Resolved the central mechanism of CHK1 activation: 9-1-1 recruits TopBP1 via phospho-Rad9 C-terminal residues to localize the ATR-activating domain, with TopBP1 bypass by AD-PCNA/H2B fusions proving the clamp's role is positional.

    Evidence Co-IP, domain-fusion bypass, phosphosite (Ser-373) mutagenesis, and CHK1 phosphorylation assays in human cells and Xenopus extracts

    PMID:17243194 PMID:17426133 PMID:17575048 PMID:17636252 PMID:17721446 PMID:17855402

    Open questions at the time
    • Kinase identity for the key C-terminal site not yet pinned (resolved later)
    • Stoichiometry of clamp:TopBP1:ATR not determined
  17. 2008 High

    Identified the RAD9 checkpoint recruitment domain binding the RPA70 OB-fold, revealed a resection-limiting role through Dot1/H3K79me, and characterized TLK1 and MLH1 interactions linking RAD9 to repair and mismatch repair.

    Evidence Domain mutagenesis with focus/CHK1 assays, ssDNA quantification (QAOS) with genetic dissection, and in vitro kinase/MMR assays with point mutants

    PMID:18418382 PMID:18842633 PMID:18936170 PMID:18940270

    Open questions at the time
    • How resection control integrates with checkpoint signaling not fully resolved
    • MMR contribution single-lab and not validated in vivo
  18. 2009 High

    Solved the atomic structure of human 9-1-1, revealing a PCNA-like toroid with a single repair-enzyme-binding site competitively blocked by p21 and a FEN1 PIP-box docking on the Rad1 IDC loop.

    Evidence X-ray crystallography from two independent labs with biochemical competition assays, plus TLK1B end-joining/release assays

    PMID:19446481 PMID:19464297 PMID:20021694

    Open questions at the time
    • Structure of DNA-bound or loaded clamp not captured
    • How enzyme handoffs at the single site are ordered unknown
  19. 2010 High

    Mapped CK2 phosphorylation of Rad9 Ser-341/Ser-387 and the TopBP1 BRCT2 docking that enable ATR activation, and identified DDK and CDK1 phosphorylation events controlling Rad9 release and cell-cycle-restricted recruitment.

    Evidence In vitro kinase assays with mutagenesis and survival assays, TopBP1 crystal structure with phosphopeptide binding, and Dpb11/CDK1 mutagenesis with checkpoint assays in yeast

    PMID:20545769 PMID:20700441 PMID:20724438 PMID:21095590

    Open questions at the time
    • Integration of multiple kinase inputs on Rad9 tail not quantified
    • Dynamics of recruitment vs release in vivo incompletely characterized
  20. 2011 Medium

    Established the Dpb11-Mec1-Rad9 ternary complex requiring CDK1-generated docking sites and identified PRMT5 arginine methylation of RAD9 as a checkpoint regulator, refining how RAD9 phosphorylation by Mec1 is enabled and cell-cycle-gated.

    Evidence In vitro reconstitution of ternary complex with CDK1 phosphosite mutagenesis, and in vitro methylation assays with site mutagenesis and CHK1/checkpoint readouts

    PMID:21321020 PMID:21946560

    Open questions at the time
    • Whether ternary complex model applies in mammals not shown
    • PRMT5 methylation single-lab and human-only
  21. 2015 Medium

    Revealed RAD9 as a negative regulator of DSB end resection by limiting Sgs1/Dna2 and retaining Mre11, identifying a counterbalancing role to its checkpoint-activating function in repair-pathway choice.

    Evidence ChIP at HO-induced DSBs with genetic epistasis and end-tethering/repair assays in yeast

    PMID:25569305 PMID:25637499

    Open questions at the time
    • Conservation of resection-limiting role in mammals not established
    • Molecular basis for nuclease inhibition incomplete
  22. 2018 Medium

    Showed checkpoint signaling is tuned by antagonists and division of labor: Slx4/Rtt107 and Sae2 limit Rad9-driven Rad53 hyperactivation, while Mrc1 and Rad9 control replication checkpoint phases through complementary mechanisms.

    Evidence Co-IP and ChIP with genetic epistasis, Rad53 phosphorylation kinetics, and DNA combing in yeast mutants

    PMID:23160493 PMID:25091155 PMID:30158111 PMID:30510002

    Open questions at the time
    • Whether these regulatory antagonists operate on mammalian RAD9A unknown
    • Quantitative thresholds for checkpoint tuning not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple post-translational inputs (CK2, c-Abl, PKCδ, TLK1, CDK1, DDK, PRMT5, caspase-3) are integrated to switch RAD9A between checkpoint-activating, repair-promoting, resection-limiting, and pro-apoptotic states in human cells remains unresolved.
  • No unified model integrating RAD9A's modifications and functional states in mammals
  • Structure of the loaded, DNA-bound human 9-1-1 with partners not determined
  • In vivo coordination of repair vs apoptotic decisions not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2 GO:0005198 structural molecule activity 2 GO:0042393 histone binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-73894 DNA Repair 4 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2
Partners
BCL2L1FEN1HUS1MLH1RAD1RAD51RPATOPBP1
Complex memberships
9-1-1 (RAD9-HUS1-RAD1) clamp

Evidence

Reading pass · 65 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 RAD9 gene product is essential for G2 cell cycle arrest in response to DNA damage in S. cerevisiae; rad9 mutant cells fail to delay division after irradiation and die, whereas wild-type cells arrest in G2 until damage is repaired. Genetic analysis of rad9 mutants, X-ray irradiation, cell cycle analysis Science High 3291120
1990 RAD9-dependent G2 arrest and recovery from arrest can occur in the presence of cycloheximide, demonstrating the mechanism is posttranslational; rad9 null mutants are viable but show elevated spontaneous chromosome loss. Cycloheximide treatment, deletion mutant construction, chromosome loss assay Molecular and cellular biology High 2247073
1993 RAD9 checkpoint is phase-specific (late S/G2) and signal-specific (DNA lesions), and RAD17 is also required for the same checkpoint; both genes are required for G2 arrest after X- or UV-irradiation. Genetic epistasis with cdc mutants, cell cycle analysis, double-mutant analysis Genetics High 8514150
1993 RAD9 is required for DNA damage-induced G1 arrest (G1/S checkpoint) in S. cerevisiae, in addition to its known G2 checkpoint role. Alpha-factor G1 synchronization, UV/gamma-irradiation, cell cycle analysis in rad9 mutants Proceedings of the National Academy of Sciences of the United States of America High 8367452
1996 RAD9 is required for DNA damage-dependent transcriptional induction of a large regulon of repair, replication, and recombination genes; this transcriptional response is cell cycle-independent. Northern blot analysis, lacZ reporter assays, RAD9 deletion mutants The EMBO journal High 8670896
1996 RAD9 and DNA polymerase epsilon (POL2) function in parallel sensory branches upstream of Rad53 for transducing the UV DNA damage checkpoint signal; both branches independently activate Mec1/Rad53. Genetic epistasis, Rad53 phosphorylation assays, RNR3 induction assays in double mutants Genes & development High 8895664
1997 RAD9, RAD17, and RAD24 are required for S-phase regulation (slowing of S-phase progression) in response to alkylation damage in S. cerevisiae, acting upstream of MEC1 and RAD53. S-phase progression assays, epistasis analysis with mec1 and rad53 mutants Genetics Medium 9017389
1998 Rad9 is hyperphosphorylated in response to DNA damage in a MEC1- and TEL1-dependent manner in S. cerevisiae; hyperphosphorylated Rad9 physically associates with Rad53 after damage. Phosphatase treatment, Western blot, co-immunoprecipitation, checkpoint gene epistasis The EMBO journal High 9755168
1998 The C-terminal FHA domain of Rad53 specifically recognizes phosphorylated Rad9; this interaction is required for DNA damage-dependent Rad53 phosphorylation and G2/M checkpoint arrest in S. cerevisiae. FHA domain mutagenesis, co-immunoprecipitation, checkpoint functional assays Science High 9657725
1998 RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway upstream of MEC1 and RAD53; the double rad9Δ-rad24Δ mutant abolishes the G1/S checkpoint and essentially eliminates transcriptional damage response. Double-mutant epistasis, checkpoint delay assays, transcriptional induction assays, Rad53 modification analysis The EMBO journal High 9564050
1999 Human Rad9, Rad1, and Hus1 form a DNA damage-responsive heterotrimeric protein complex; hRad9 is phosphorylated in response to DNA damage. Co-immunoprecipitation of human proteins, DNA damage treatment The Journal of biological chemistry Medium 9872989
1999 The BRCT domain of yeast Rad9 mediates Rad9-Rad9 homo-oligomerization, preferentially interacting with hyperphosphorylated Rad9; BRCT mutations abolish Rad9 hyperphosphorylation, Rad53 phosphorylation, and checkpoint function. Two-hybrid, in vitro and in vivo co-immunoprecipitation, BRCT point mutagenesis, checkpoint survival assays Current biology : CB High 10339432
2000 Structure predictions indicate Rad9, Rad1, and Hus1 each share a PCNA-like fold and form a heterotrimeric ring analogous to the PCNA sliding clamp; Rad17 has RFC-like ATPase clamp-loader properties. Computational fold recognition, comparative modeling, generalized sequence profiles Nucleic acids research Low 10871397
2000 S. pombe Hus1 forms a stable complex with Rad9 and Rad1 in vivo; Hus1 nuclear localization depends on Rad17. Co-immunoprecipitation, fractionation, indirect immunofluorescence Molecular and cellular biology Medium 10648611
2000 Human RAD9 interacts with the anti-apoptotic proteins BCL-2 and BCL-xL (but not pro-apoptotic BAX/BAD) and overexpression induces apoptosis that can be blocked by BCL-2 or BCL-xL; antisense RAD9 suppresses DNA damage-induced cell death. Yeast two-hybrid, co-immunoprecipitation, overexpression in mammalian cells, antisense knockdown Nature cell biology High 10620799
2000 Solution structure of Rad53 FHA1 domain determined; a phospho-Thr peptide from Rad9 (pThr-192, motif pTXXD) binds FHA1 with Kd ~0.36 μM, identifying the molecular basis for Rad9-Rad53 interaction. NMR structure determination, peptide library screening, surface plasmon resonance Journal of molecular biology High 11124038
2001 Yeast Rad9 forms two distinct large complexes: a >850 kDa complex with hypophosphorylated Rad9 in undamaged cells, and a 560 kDa complex with hyperphosphorylated Rad9 and Rad53 after damage. The 560 kDa complex catalyzes Rad53 activation via Rad53 in trans autophosphorylation (scaffold mechanism); this requires Rad53 kinase activity but not Mec1/Tel1 once the complex forms. Gel filtration, co-immunoprecipitation, in vitro kinase reconstitution assays Molecular cell High 11511366
2001 In S. pombe, the Hus1-Rad1-Rad9 complex has PCNA-like structural and functional features; mutations designed using the PCNA alignment identify functionally important residues, though the complex also has unique features distinct from PCNA. Structure-function mutagenesis, checkpoint assays in fission yeast Molecular biology of the cell Medium 11739777
2002 Human Rad17 recruits the Rad9 complex (9-1-1) onto chromatin after DNA damage; Rad17 binds chromatin prior to damage and is phosphorylated by ATR on chromatin after damage; Rad17 phosphorylation is not required for Rad9 loading; Hus1 is required for damage-induced Rad17 phosphorylation. Chromatin fractionation, co-immunoprecipitation, kinase inhibition, siRNA knockdown Genes & development High 11799063
2002 Multiple Mec1/Tel1 consensus [S/T]Q sites within yeast Rad9 are phosphorylated in response to DNA damage; these Rad9 phosphorylation sites are selectively required for Rad53 (not Chk1) branch activation; phospho-Rad9 peptides bind Rad53 FHA domains in vitro. Site-directed mutagenesis of SQ sites, in vitro FHA domain pulldown with phosphopeptides, checkpoint functional assays Molecular cell High 12049741
2002 Electron microscopy of reconstituted human 9-1-1 complex reveals a ring structure indistinguishable in shape and size from PCNA; Rad17-RFC forms an oval clamp-loader complex with ATPase activity and binds Rad9-1-1. Baculovirus reconstitution, electron microscopy, native molecular mass determination, ATPase assay Genes to cells : devoted to molecular & cellular mechanisms High 12167163
2002 c-Abl tyrosine kinase constitutively binds Rad9 via its SH3 domain interacting with the Rad9 C-terminal region; c-Abl phosphorylates Rad9 at Tyr-28 (BH3 domain) in vitro and in cells exposed to DNA damage, inducing Rad9 binding to Bcl-xL and contributing to apoptosis. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (Tyr-28), apoptosis assays Molecular and cellular biology High 11971963
2002 Genotoxin-induced 9-1-1 chromatin binding does not require Rad9 Ser-272 phosphorylation, DNA replication, or ATM/ATR/DNA-PK catalytic activity, indicating chromatin binding is a proximal, kinase-independent event in checkpoint signaling. Chromatin fractionation, PIKK inhibitors, phosphorylation site mutants, replication inhibitors The Journal of biological chemistry High 12228248
2003 Protein kinase Cδ (PKCδ) associates with human Rad9 and phosphorylates it in vitro and in cells after genotoxic stress; PKCδ activation is required for formation of the Rad9-Hus1-Rad1 complex and for Rad9 binding to Bcl-2; inhibition of PKCδ attenuates Rad9-mediated apoptosis. Co-immunoprecipitation, in vitro kinase assay, PKCδ inhibitor, checkpoint/apoptosis assays The EMBO journal High 12628935
2003 Phosphorylation of Rad9 C-terminal tail residues (beyond Ser-272) is essential for Chk1 activation following HU, IR, and UV treatment; the Rad9 phospho-tail drives S-phase checkpoint arrest; cells with phosphorylation-deficient Rad9 are as UV/HU sensitive as Rad9-null cells. Site-directed mutagenesis of nine phosphorylation sites, complementation of Mrad9-/- ES cells, checkpoint assays The Journal of biological chemistry High 12709442
2004 Human RAD9 can directly bind a p53 consensus DNA-binding sequence in the p21 promoter and transactivate p21 transcription; RAD9 overexpression increases p21 RNA and protein levels. Luciferase reporter assay, EMSA, overexpression, Northern blot, microarray Proceedings of the National Academy of Sciences of the United States of America Medium 15184659
2004 The 9-1-1 complex physically interacts with DNA polymerase beta in vitro and stimulates its activity, increasing affinity for primer-template and stimulating displacement synthesis; this effect is specific to Pol beta and not Pol lambda, Pol alpha, or Pol delta. In vitro pulldown, DNA polymerase activity assays, gel shift assays Nucleic acids research High 15314187
2004 The 9-1-1 complex binds and stimulates Flap Endonuclease 1 (FEN1) on flap, nick, and gapped substrates; stimulation is distinct from PCNA stimulation and cannot substitute for PCNA in stimulating Pol beta. In vitro binding assay, FEN1 nuclease activity assays on multiple substrates Proceedings of the National Academy of Sciences of the United States of America High 15556996
2004 Mammalian Rad9 deletion sensitizes cells to camptothecin, etoposide, and cytarabine; Rad9 is required for cytarabine-induced S-phase checkpoint but not for camptothecin/etoposide S-phase checkpoint; Rad9's predominant role in ES cells is promoting survival after replication stress. Rad9-/- ES cells, clonogenic survival, S-phase checkpoint assays ([3H]thymidine incorporation, Cdc25A), apoptosis assays The Journal of biological chemistry Medium 14988409
2004 A specific N-terminal domain of yeast Rad9 (Chk1 activation domain, CAD) is required for Chk1 phosphorylation/activation but not for Rad53 activation, demonstrating that Rad9 activates Rad53 and Chk1 through separable domains. Rad9 domain deletion analysis, Chk1 and Rad53 phosphorylation assays, checkpoint functional assays Journal of cell science Medium 14709724
2004 Mec1 phosphorylates Rad9 at S/TQ motifs in vitro and promotes Rad9 accumulation at double-strand breaks (DSBs) in vivo; multiple SQ motif mutations reduce Rad9 association with DSBs; Rad9 association with DSBs is required for full Rad9 phosphorylation and Rad9-Rad53 interaction. ChIP assay, in vitro kinase assay (Mec1), mec1 mutants, SQ motif mutagenesis Molecular and cellular biology High 15060150
2004 Mouse Rad9 (Mrad9) deletion causes embryonic lethality at midgestation; Mrad9-/- cells show increased chromosome aberrations, HPRT mutations, and extreme sensitivity to UV, gamma rays, and hydroxyurea; ectopic expression of Mrad9 or human HRAD9 complements these defects. Targeted gene deletion, embryonic stem cell analysis, clonogenic survival, mutation frequency, complementation Molecular and cellular biology High 15282322
2005 Dot1-dependent methylation of histone H3 Lys79 is required for Rad9 binding to DSBs and for Rad53 phosphorylation in G1 and S-phase checkpoints; mutation of the Rad9 Tudor domain (responsible for binding methylated H3K79) phenocopies the dot1Δ checkpoint defect. Checkpoint assays in dot1Δ/H3K79 mutants, Rad9 Tudor domain mutagenesis, Rad53 phosphorylation, DSB binding assays Molecular and cellular biology High 16166626
2005 Yeast Rad9 acts as a bona fide signaling adaptor (not scaffold) that enables efficient, direct phosphorylation of Rad53 by Mec1 through a phospho- and FHA-dependent Rad9-Rad53 interaction; Rad9 stimulates Mec1 to phosphorylate Rad53 in biochemical reconstitution. Biochemical reconstitution with purified Rad9, Rad53 phosphorylation mapping by mass spectrometry, in vitro kinase assays Current biology : CB High 16085488
2005 RAD9-Hus1-Rad1 (9-1-1) interacts with RPA in human cells; Rad9 binds both RPA70 and RPA32 subunits; UV/camptothecin stimulate 9-1-1/RPA interaction; RPA siRNA knockdown blocks damage-dependent chromatin association of 9-1-1 and 9-1-1 complex formation. Co-immunoprecipitation, siRNA knockdown, nuclear focus colocalization, chromatin fractionation Oncogene Medium 15897895
2006 Mammalian Rad9 interacts with Rad51; Mrad9 inactivation leads to increased telomere end-to-end associations, telomere loss, delayed gamma-H2AX focus kinetics, and reduced homologous recombination repair, indicating a role in HR and telomere stability. Co-immunoprecipitation, HR repair assays, telomere FISH, gamma-H2AX focus analysis, Rad9 conditional knockdown Molecular and cellular biology Medium 16479004
2006 The 9-1-1 complex (via Rad9 and Hus1 individually and as complex) interacts with and stimulates NEIL1 DNA glycosylase activity; Rad9 and NEIL1 colocalize to nuclear foci in H2O2-treated cells. Co-immunoprecipitation, in vitro glycosylase stimulation assay, immunofluorescence co-localization Nucleic acids research Medium 17395641
2006 The mammalian 9-1-1 complex localizes to telomeres and associates with catalytically competent telomerase; Hus1-deficient cells show severe telomere shortening; 9-1-1 positively regulates telomerase DNA polymerase activity. Telomere length measurement (Q-FISH), telomerase activity assay, co-immunoprecipitation with telomerase Current biology : CB Medium 16890531
2007 Rad9's role in Chk1 activation is to recruit TopBP1 to the replication fork; the 9-1-1 clamp's primary function is to localize the ATR-activating domain (AD) of TopBP1 via direct Rad9-TopBP1 binding; fusion of AD to PCNA or H2B bypasses the 9-1-1 requirement. Co-immunoprecipitation, domain fusion experiments, Chk1 phosphorylation assays Genes & development High 17575048
2007 In Xenopus egg extracts, the C-terminal domain of Rad9 interacts with BRCT I-II of TopBP1 via phosphorylation of Ser-373; this interaction is required for ATR-ATRIP binding to TopBP1's activating domain and for checkpoint signaling; Rad9 Ser-373-Ala and TopBP1 ΔBRCT I-II mutants are checkpoint defective. Xenopus egg extract biochemistry, co-immunoprecipitation, phospho-mutant analysis, Rad9 C-terminal fragment inhibitor The Journal of biological chemistry High 17636252
2007 Rad9 BRCT domain directly interacts with phosphorylated histone H2A in vitro; a Rad9 point mutation abolishing this interaction causes G1 checkpoint defects similar to H2A phosphorylation site mutation; the Tudor domain mediates constitutive chromatin association while BRCT domain-pH2A interaction enables damage-specific G1 arrest. In vitro BRCT-phospho-H2A binding assay, point mutagenesis, G1 checkpoint assays EMBO reports High 17721446
2007 The Rad9 Tudor domain binds to histone H3 methylated at Lys79 (H3K79me) in vitro and is required for Rad9 focal accumulation after DNA damage; Tudor-H3K79me interaction functions in G1 checkpoint activation and G2 DSB repair. In vitro Tudor domain-H3K79me binding assay, Rad9 Tudor mutants, checkpoint assays, focus formation Yeast (Chichester, England) High 17243194
2007 The 9-1-1 complex interacts with and stimulates human TDG glycosylase; Rad9-TDG interaction is enhanced after MNNG treatment; Hus1 binding domain mapped to TDG residues 67-110. Co-immunoprecipitation, glycosylase activity assay, domain mapping mutagenesis, co-localization Nucleic acids research Medium 17855402
2007 The 9-1-1 complex interacts with APE1 in vitro and in vivo and stimulates APE1 AP-endonuclease activity; the 9-1-1 complex enhances long-patch base excision repair (LP-BER) reconstituted in vitro by specifically stimulating APE1 and Pol beta. In vitro co-immunoprecipitation, APE1 endonuclease assay, LP-BER reconstitution assay Nucleic acids research High 17426133
2008 Dot1 histone methyltransferase and Rad9 (via Tudor domain binding to H3K79me) inhibit DNA end resection at DSBs and uncapped telomeres; loss of Rad9 or Dot1 leads to faster ssDNA accumulation at DSBs via a Rad50-dependent nuclease, accelerating Mec1 activation. ssDNA quantification (QAOS), genetic analysis of dot1Δ and rad9 mutants, DSB resection kinetics The EMBO journal High 18418382
2008 The basic cleft of RPA70 N-terminal OB-fold domain binds RAD9 via an acidic peptide in the RAD9 C-terminal tail (checkpoint recruitment domain, CRD); mutation of the RAD9 CRD impairs its localization to damage sites without affecting 9-1-1 complex formation or TopBP1 binding; RAD9-RPA interaction is required for ATR signaling to CHK1. Domain mutagenesis, co-immunoprecipitation, nuclear focus formation assays, Chk1 phosphorylation assay Molecular and cellular biology High 18936170
2008 TLK1B phosphorylates human Rad9 at S328; TLK1B overexpression hastens DSB repair and modulates the amount of 9-1-1 at DSBs; Rad9 competes with chromatin assembly factor Asf1 for TLK1B binding. In vitro kinase assay, co-immunoprecipitation, ChIP at HO-induced DSB, complementation in Rad9-null cells DNA repair Medium 18940270
2008 Rad9 plays a role in DNA mismatch repair through direct physical interaction with MLH1; a single-point mutation in Rad9 disrupting MLH1 interaction significantly reduces MMR activity without affecting checkpoint functions. Co-immunoprecipitation, MMR activity assay, single-point mutagenesis, checkpoint assays Nucleic acids research Medium 18842633
2009 Crystal structure of human 9-1-1 complex determined at 3.2 Å (Doré et al.) and at 2.5 Å (Sohn and Cho); the complex forms a toroidal heterotrimeric ring similar to PCNA with a single repair enzyme-binding site on 9-1-1 that can be competitively blocked by p21(cip1/waf1); FEN1 PIP box binds to the IDC loop of Rad1. X-ray crystallography, biochemical competition assays Molecular cell High 19446481 19464297
2009 TLK1B promotes repair of DSB ends with incompatible termini through its interaction with Rad9; Rad9 is important for processing ends prior to ligation; TLK1B's kinase activity is required for timely release of Rad17 and Rad9 from the DSB after repair. In vitro plasmid ligation assay, Rad9 immunodepletion, HO-cleavage system, ChIP BMC molecular biology Medium 20021694
2010 Crystal structure of the N-terminal region of human TopBP1 reveals a triple-BRCT domain; pSer387 of Rad9 (phosphorylated by CK2) specifically interacts with the second (but not third) BRCT domain of TopBP1. X-ray crystallography, phosphopeptide binding assay Nucleic acids research High 20724438
2010 Casein kinase 2 (CK2) phosphorylates Rad9 at Ser-341 and Ser-387 in the C-terminal tail; phosphorylation at both sites is required for efficient interaction with TopBP1 in vitro; CK2 phosphorylation is required in vivo and cells expressing phospho-deficient Rad9 are hypersensitive to UV and MMS. In vitro kinase assay with CK2, site-directed mutagenesis, co-immunoprecipitation, clonogenic survival Genes to cells : devoted to molecular & cellular mechanisms High 20545769
2010 In fission yeast, DDK (Hsk1/Cdc7) phosphorylates Rad9 in response to replication-induced DNA damage; Rad9 phosphorylation by DDK is dependent on prior Rad3(ATR) phosphorylation and disrupts Rad9-RPA interaction, promoting release of Rad9 from DNA damage sites to facilitate repair. Kinase assays, phosphorylation-deficient mutants, DNA repair foci assays, co-immunoprecipitation Molecular cell High 21095590
2010 In S. cerevisiae, CDK1-dependent phosphorylation of Rad9 on Ser11 creates a binding site for Dpb11, enabling a chromatin-binding-independent pathway for Rad53 activation; BRCT domain-mediated Rad9 dimerization is required for chromatin binding and checkpoint function in G1 and M phases. CDK1 phosphorylation site mutagenesis, Dpb11 interaction assays, BRCT domain mutants, artificial dimerization with GST/FKBP fusions, checkpoint assays PLoS genetics High 20700441
2011 Dpb11 forms a ternary complex with Mec1 and Rad9, required for efficient Rad9 phosphorylation by Mec1 in vitro and checkpoint activation in vivo; CDK1 phosphorylates Rad9 on two key residues, generating a Dpb11 BRCT-binding site for Rad9 recruitment into the ternary complex; this ensures checkpoint signaling is restricted to non-G1 phases. In vitro kinase assay with reconstituted ternary complex, CDK1 phosphosite mutagenesis, Dpb11 interaction assays, checkpoint assays The EMBO journal High 21946560
2011 Human Rad9 is methylated by PRMT5 (protein arginine methyltransferase 5); arginine methylation of Rad9 is required for S/M and G2/M checkpoint activation and Chk1 activation; methylation-deficient Rad9 increases cellular sensitivity to DNA damage. Co-immunoprecipitation, in vitro methylation assay, arginine methylation site mutagenesis, Chk1 phosphorylation assays, checkpoint and survival assays Nucleic acids research Medium 21321020
2012 DNA-repair scaffolds Slx4 and Rtt107 prevent hyperactivation of checkpoint signaling by competing with the Rad9 adaptor; Slx4-Rtt107 complex physically interacts with Dpb11 and phospho-H2A, thereby reducing Rad9-dependent Rad53 activation; loss of Slx4 or Rtt107 causes Rad53 hyperactivation. Co-immunoprecipitation, epistasis with rad53/H2A hypomorphs, Rad53 phosphorylation assays Nature High 23160493
2012 Stable reduction of Rad9 in prostate cancer cells impairs migration, invasion, and anchorage-independent growth; Rad9 promotes anoikis resistance by maintaining integrin β1 expression and Akt activation; Mrad9 expression in Rad9-knockdown cells restores these phenotypes. siRNA and stable shRNA knockdown, migration/invasion assays, anchorage-independent growth, anoikis assays, Akt activation measurements The Journal of biological chemistry Medium 23066031
2013 TLK1 phosphorylates Rad9 at Thr355 in vitro and in vivo; this phosphorylation is reduced upon ionizing radiation exposure; TLK1 depletion causes prolonged G2/M arrest after IR, phenocopied by Rad9-T355A overexpression; TLK1 and Chk1 act together to modulate Rad9 phosphorylation status. In vitro kinase assay, phospho-specific analysis, siRNA depletion, T355A mutant overexpression, cell cycle analysis PloS one Medium 24376897
2014 The 9-1-1/TopBP1 interaction and ATR activation create a positive feedback loop: 9-1-1 and TopBP1 independently recruit to UV-damage sites, then direct interaction of phospho-Rad9 with TopBP1 activates ATR, which in turn promotes further TopBP1 accumulation at damage sites. Laser UV-microirradiation, live-cell focus analysis, TopBP1-binding-deficient Rad9 mutant, ATR kinase inhibitor DNA repair Medium 25091155
2015 Yeast Rad9 limits the action of Sgs1/Dna2 at DSBs by inhibiting Sgs1 binding at DSB ends; deletion of RAD9 reduces Mre11 binding to DSBs and restores DSB end-tethering and efficient repair in cells lacking Sae2 or with nuclease-deficient MRX. ChIP at HO-induced DSB, genetic epistasis with sgs1-ss mutant, DSB repair assays EMBO reports Medium 25637499
2015 Rad9 (yeast 53BP1 ortholog) promotes Mre11 retention at persistent DSBs; deletion of RAD9 reduces Mre11 binding, facilitates Rad52 recruitment, and restores end-tethering and repair via an Sgs1-dependent mechanism in sae2Δ cells. ChIP, genetic epistasis, DSB repair and end-tethering assays PLoS genetics Medium 25569305
2018 Sae2 counteracts Rad9 accumulation at DSBs by competing for Tel1 phosphorylation substrates, thereby reducing Rad9 binding to chromatin and to Rad53; this function is independent of Mre11 nuclease activity. ChIP at DSBs, epistasis analysis, Rad53 phosphorylation assays, Tel1 substrate competition analysis Proceedings of the National Academy of Sciences of the United States of America Medium 30510002
2018 Mrc1 and Rad9 control DNA replication through complementary mechanisms: Mrc1 rapidly activates Rad53 at stalled forks to repress late-firing origins, while Rad9 takes over to maintain sustained checkpoint signaling; Rad9-mediated Rad53 activation slows fork progression. DNA combing, origin firing analysis, Rad53 phosphorylation kinetics, genetic epistasis between mrc1 and rad9 mutants The EMBO journal Medium 30158111
2003 Caspase-3 cleaves human Rad9 at multiple sites; cleavage results in translocation of the N-terminal BH3-containing fragment from nucleus to cytosol, where it binds Bcl-XL and promotes apoptosis; cleavage-resistant Rad9 DDD/AAA mutant protects cells from DNA damage-induced apoptosis. In vitro caspase-3 cleavage assay, site-directed mutagenesis, caspase inhibitors, caspase-3-deficient MCF-7 cells, immunofluorescence, apoptosis assays Oncogene High 14508514

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
2002 Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes & development 422 11799063
2007 The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes & development 388 17575048
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 257 15279787
2001 Budding yeast Rad9 is an ATP-dependent Rad53 activating machine. Molecular cell 249 11511366
2005 Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Molecular and cellular biology 241 16166626
1993 Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 241 8514150
1998 The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1-dependent hyperphosphorylation and interacts with Rad53 after DNA damage. The EMBO journal 233 9755168
2007 The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. The Journal of biological chemistry 232 17636252
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
1990 Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationally in cell cycle arrest after DNA damage. Molecular and cellular biology 202 2247073
2005 Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Current biology : CB 195 16085488
2002 Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Molecular cell 194 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 184 8367452
1997 RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage. Genetics 169 9017389
1999 Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex. The Journal of biological chemistry 168 9872989
2008 Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. The EMBO journal 163 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
2003 Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9. The EMBO journal 131 12628935
1989 Cloning and sequence analysis of the Saccharomyces cerevisiae RAD9 gene and further evidence that its product is required for cell cycle arrest induced by DNA damage. Molecular and cellular biology 130 2664461
1998 RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation. The EMBO journal 128 9564050
2007 Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast. EMBO reports 126 17721446
2000 Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis. Nature cell biology 122 10620799
2006 Mammalian Rad9 plays a role in telomere stability, S- and G2-phase-specific cell survival, and homologous recombinational repair. Molecular and cellular biology 118 16479004
2004 Deletion of mouse rad9 causes abnormal cellular responses to DNA damage, genomic instability, and embryonic lethality. Molecular and cellular biology 107 15282322
2011 Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. The EMBO journal 106 21946560
2006 Histone H2A phosphorylation and H3 methylation are required for a novel Rad9 DSB repair function following checkpoint activation. DNA repair 105 16650810
1996 A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription. The EMBO journal 104 8670896
2004 The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair. Nucleic acids research 103 15314187
2009 Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation. Molecular cell 102 19446481
2004 ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage. Cell cycle (Georgetown, Tex.) 101 15190204
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 94 25569305
2005 Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells. Oncogene 93 15897895
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 83 23160493
2006 Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1. The Biochemical journal 82 16879101
2002 c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage. Molecular and cellular biology 80 11971963
1999 The BRCT domain of the S. cerevisiae checkpoint protein Rad9 mediates a Rad9-Rad9 interaction after DNA damage. Current biology : CB 78 10339432
2002 Clamp and clamp loader structures of the human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC. Genes to cells : devoted to molecular & cellular mechanisms 77 12167163
2009 Structure and functional implications of the human rad9-hus1-rad1 cell cycle checkpoint complex. The Journal of biological chemistry 71 19535328
2000 Structure of the FHA1 domain of yeast Rad53 and identification of binding sites for both FHA1 and its target protein Rad9. Journal of molecular biology 67 11124038
2011 A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage. Nucleic acids research 66 21321020
2010 Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1. Nucleic acids research 66 20724438
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
2007 The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. Nucleic acids research 65 17395641
1993 A novel mutation in DNA topoisomerase I of yeast causes DNA damage and RAD9-dependent cell cycle arrest. Genetics 65 8385050
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
2010 Dynamics of Rad9 chromatin binding and checkpoint function are mediated by its dimerization and are cell cycle-regulated by CDK1 activity. PLoS genetics 61 20700441
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
2005 The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity. Journal of molecular biology 60 16216273
1996 The rad9 gene of Coprinus cinereus encodes a proline-rich protein required for meiotic chromosome condensation and synapsis. Genetics 59 8846891
2005 The cell cycle checkpoint gene Rad9 is a novel oncogene activated by 11q13 amplification and DNA methylation in breast cancer. Cancer research 57 16204032
2015 Escape of Sgs1 from Rad9 inhibition reduces the requirement for Sae2 and functional MRX in DNA end resection. EMBO reports 55 25637499
2010 A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions. Journal of molecular biology 55 20816984
2007 The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase. Nucleic acids research 55 17855402
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
2018 Mrc1 and Rad9 cooperate to regulate initiation and elongation of DNA replication in response to DNA damage. The EMBO journal 52 30158111
2013 Conditional inactivation of the DNA damage response gene Hus1 in mouse testis reveals separable roles for components of the RAD9-RAD1-HUS1 complex in meiotic chromosome maintenance. PLoS genetics 50 23468651
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
1992 Molecular cloning and analysis of Schizosaccharomyces pombe rad9, a gene involved in DNA repair and mutagenesis. Molecular & general genetics : MGG 47 1588907
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 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
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
2008 Rad9 has a functional role in human prostate carcinogenesis. Cancer research 42 18316588
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
2004 Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication. Genes to cells : devoted to molecular & cellular mechanisms 38 15066121
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
2014 Interaction between Rad9-Hus1-Rad1 and TopBP1 activates ATR-ATRIP and promotes TopBP1 recruitment to sites of UV-damage. DNA repair 33 25091155
2010 DDK phosphorylates checkpoint clamp component Rad9 and promotes its release from damaged chromatin. Molecular cell 33 21095590
2008 ATR and Rad17 collaborate in modulating Rad9 localisation at sites of DNA damage. Journal of cell science 32 19020305
2002 Involvement of RAD9-dependent damage checkpoint control in arrest of cell cycle, induction of cell death, and chromosome instability caused by defects in origin recognition complex in Saccharomyces cerevisiae. Eukaryotic cell 32 12455955
2008 Identification of androgen-selective androgen-response elements in the human aquaporin-5 and Rad9 genes. The Biochemical journal 31 18215141
2013 Tousled-like kinase-dependent phosphorylation of Rad9 plays a role in cell cycle progression and G2/M checkpoint exit. PloS one 30 24376897
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
2003 Caspase-3-mediated cleavage of Rad9 during apoptosis. Oncogene 30 14508514

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