title: The checkpoint clamp protein Rad9 facilitates DNA-end resection and prevents alternative non-homologous end joining.
abstract: DNA damage activates the cell cycle checkpoint to regulate cell cycle progression. The checkpoint clamp (Rad9-Hus1-Rad1 complex) is recruited to damage sites, and is required for checkpoint activation. While functions of the checkpoint clamp in checkpoint activation have been well studied, its functions in DNA repair regulation remain elusive. Here we show that Rad9 is required for efficient homologous recombination (HR), and facilitates DNA-end resection. 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 (altNHEJ). These findings reveal novel function of the checkpoint clamp in HR.
authors.affiliation: a Department of Radiation Oncology ; Johns Hopkins University School of Medicine ; Baltimore MD USA.
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Tsai
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kai
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004265:DNA Helicases / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051716:Replication Protein A / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D051716:Replication Protein A; C069930:rad9 protein; C516794:RPA2 protein, human; D004265:DNA Helicases; C509908:DNA2 protein, human
keywords: ATM, ataxia-telangiectasia-mutated; ATR, ataxia telangiectasia and Rad3-related; DNA repair; DSB, Double-strand break; HR, homologous recombination; altNHEJ, alternative non-homologous recombination; cell cycle checkpoint; homologous recombination