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.
Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Xiaochun
X
Yu
Junjie
J
Chen
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