Cdk1 Protein-mediated Phosphorylation of Receptor-associated Protein 80 (RAP80) Serine 677 Modulates DNA Damage-induced G2/M Checkpoint and Cell Survival
Copyright policy )Cdk1 Protein-mediated Phosphorylation of Receptor-associated Protein 80 (RAP80) Serine 677 Modulates DNA Damage-induced G2/M Checkpoint and Cell Survival
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.
- Hanyang University Korea (Republic of)
- Sungkyunkwan University Korea (Republic of)
- Sungkyul University Korea (Republic of)
- UNIST (Ulsan National Institute of Science and Technology) Korea (Republic of)
Cell Survival, Mutation, Missense, Nuclear Proteins, DNA-Binding Proteins, G2 Phase Cell Cycle Checkpoints, Amino Acid Substitution, CDC2 Protein Kinase, Serine, Humans, M Phase Cell Cycle Checkpoints, Histone Chaperones, Cyclin B1, Phosphorylation, Carrier Proteins, Protein Processing, Post-Translational, DNA Damage, HeLa Cells
Cell Survival, Mutation, Missense, Nuclear Proteins, DNA-Binding Proteins, G2 Phase Cell Cycle Checkpoints, Amino Acid Substitution, CDC2 Protein Kinase, Serine, Humans, M Phase Cell Cycle Checkpoints, Histone Chaperones, Cyclin B1, Phosphorylation, Carrier Proteins, Protein Processing, Post-Translational, DNA Damage, HeLa Cells
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