title: Cdk1 protein-mediated phosphorylation of receptor-associated protein 80 (RAP80) serine 677 modulates DNA damage-induced G2/M checkpoint and cell survival.
abstract: Post-translational phosphorylation plays critical roles in the assembly of signaling and repair proteins in the DNA damage response pathway. RAP80, a component of the BRCA1-A complex, is crucial in cell cycle checkpoint activation and DNA damage repair. However, its molecular mechanism is unclear. In this study, we identified Cdk1 as a new RAP80-binding protein and demonstrated that the Cdk1-cyclin B(1) complex phosphorylates RAP80 at Ser-677 using an in vitro kinase assay and a phosphopeptide-specific antibody against phospho-Ser-677 of RAP80. RAP80 Ser-677 phosphorylation occurred in the M phase of the cell cycle when Cdk1 was in an active state. In addition, ionizing radiation (IR) induced RAP80 phosphorylation at Ser-677. Mutation of Ser-677 to alanine sensitized cells to IR and functioned in G(2)/M checkpoint control. These results suggest that post-translational phosphorylation of RAP80 by the Cdk1-cyclin B(1) complex is important for RAP80 functional sensitivity to IR and G(2)/M checkpoint control.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Hanyang University, Seoul 133-791, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Oh
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Han
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Nam Soo
authors.initials: NS
authors.lastname: Lee
authors.forename: Won-Ju
authors.initials: WJ
authors.lastname: Kim
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Hongtae
authors.initials: H
authors.lastname: Kim
mesh_terms: D019943:Amino Acid Substitution; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins; D059565:G2 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D056488:Histone Chaperones; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012694:Serine
chemical_list: C534699:CCNB1 protein, human; D002352:Carrier Proteins; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009687:Nuclear Proteins; C466234:UIMC1 protein, human; D012694:Serine; D016203:CDC2 Protein Kinase