DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains.
The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho-protein binding domain. We demonstrate here that a CTBP-interacting protein CtIP interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner. The CtIP/BRCA1 complex only exists in G(2) phase and is required for DNA damage-induced Chk1 phosphorylation and the G(2)/M transition checkpoint. However, the CtIP/BRCA1 complex is not required for the damage-induced G(2) accumulation checkpoint, which is controlled by a separate BRCA1/BACH1 complex. Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage.
Yu
Xiaochun
X
Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Chen
Junjie
J
D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004706:Endodeoxyribonucleases; D004789:Enzyme Activation; D016195:G2 Phase; D006801:Humans; D046912:Multiprotein Complexes; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference
D019313:BRCA1 Protein; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human