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The authors show that human Cyclin-Dependent-Kinases (CDKs) target the RAD9 subunit of the 9-1-1 checkpoint clamp on Thr292, to modulate DNA damage checkpoint activation. Thr292 phosphorylation on RAD9 creates a binding site for Polo-Like-Kinase1 (PLK1), which phosphorylates RAD9 on Thr313.
TLK1B mediated phosphorylation of Rad9 regulates its nuclear/cytoplasmic localization and cell cycle checkpoint
RAD9 has a prominent role in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.
these results demonstrate a positive feedback loop involving Rad9A-dependend activation of Chk1.
Intramolecular binding of the rad9 C-terminus in the checkpoint clamp Rad9-Hus1-Rad1 is closely linked with its DNA binding.
The role of Rad9 in homologous recombination is independent of its function in checkpoint activation, and this function is important for preventing alternative non-homologous end joining.
we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation
These data reveal that human Rad9 interacts directly with N-terminal region of human MYH.
Downregulation of RAD9 when combined with ionizing radiation results in reduction of ITGB1 protein levels in prostate cancer cells, and increased lethality.
Loss of hrad9 expression is associated with breast and lung cancer.
These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction.
Tousled-like kinase-dependent phosphorylation of Rad9 plays a role in cell cycle progression and G2/M checkpoint exit.
Loss of Rad9 alters expression of nucleotide excision repair factors.
Rad9, Rad17, TopBP1 and claspin play essential roles in heat-induced activation of ATR kinase and heat tolerance.
cyclin A-Cdk2 regulates apoptosis through a mechanism that involves Rad9phosphorylation
Rad9 contributes to prostate tumorigenesis by increasing not only tumor proliferation and survival but also tumor migration and invasion, anoikis resistance, and anchorage-independent growth
the affinity of Rad9 to TopBP1 correlates with the activation of the cellular DNA damage response and survival after DNA damage in HeLa cells.
Data show models for the ternary PCNA/FEN1/DNA and Rad9-Rad1-Hus1 (9-1-1 complex)/FEN1/DNA assemblies.
A review of the many activities assigned to Rad9, and speculation as to which influence its function in tumor development.
The RAD9 is loaded to damaged sites where it serves as a platform for the selective recruitment of checkpoint and repair proteins.
Rad9a is indispensable for spermatogonia differentiation and testicular development in mice.
We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells
RAD9A is essential for male fertility and for repair of DNA double-strand breaks during meiotic prophase I.
HUS1 acts as a component of the canonical 9-1-1 complex during meiotic prophase I to promote DSB repair and further propose that RAD1 and TOPBP1 respond to unsynapsed chromatin through an alternative mechanism that does not require RAD9 or HUS1.
Data show that Rad9 plays dual roles in generating functional antibodies and in maintaining the integrity of the whole genome in B cells.
Rad9A-mediated Claspin localization is a vital step during checkpoint activation.
tousled-like kinases play important roles in DNA repair, not only by modulation of chromatin assembly via Asf1, but also by a more direct function in processing the ends of a tousled-like kinase via interaction with Rad9.
HRAD9 and Mrad9 are part of a gene family and reveal a new genetic element encoding a product that interacts with multiple, known cell cycle checkpoint control proteins.
Results establish mouse rad9 as a key mammalian genetic element of pathways that regulate the cellular response to DNA damage, maintenance of genomic integrity, and proper embryonic development.
The encoded mammalian proteins participate in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, and apoptosis.
Rad9 levels are high in prostate cancer cells due at least in part to aberrant methylation or gene amplification
Mrad9 plays an important role in maintaining genomic stability and preventing tumor development in keratinocytes
These results suggest that phosphorylation of Rad9 plays a critical role in the activation of the S phase/Mitosis checkpoint, and that downstream proteins cdc2 and 14-3-3sigma mediate this function.
Rad9 is a signal in the earlier stage of epithelial cell cycle regulation and plays protective roles in alveolar epithelial cells in the pathogenesis of acute lung injury.
Disruption of the Rad9-MLH1 interaction by a single-point mutation in Rad9 leads to significantly reduced DNA mismatch repair activity.
MiR-2425-5p targets RAD9A and MYOG to regulate the proliferation and differentiation of bovine skeletal muscle-derived satellite cells.
Data show that Rad17 mediates the interaction of the Rad9-Hus1-Rad1 (9-1-1) complex with the ATR-activating protein TopBP1 in Xenopus egg extracts.
interaction of the 9-1-1 complex (Rad9-Hus1-Rad1) with the BRCT I-II region of TopBP1 is necessary for binding of ATR-ATRIP to the ATR-activating domain of TopBP1 and the ensuing activation of ATR
TopBP1 and DNA polymerase-alpha directly recruit the 9-1-1 complex (rad9-rad1-Hus1) to stalled DNA replication forks.
This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
DNA repair exonuclease rad9 homolog A
, cell cycle checkpoint control protein RAD9A
, RAD9 homolog A (S. pombe)
, cell cycle checkpoint control protein RAD9A-like
, Rad9-like protein
, RAD9 homolog A
, PCNA-like DNA checkpoint protein Rad9
, RAD9 checkpoint clamp component A L homeolog