title: The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation.
abstract: Following DNA damage cells initiate cell cycle checkpoints to allow time to repair sustained lesions. Rad9, Rad1, and Hus1 proteins form a toroidal complex, termed the 9-1-1 complex, that is involved in checkpoint signaling. 9-1-1 shares high structural similarity to the DNA replication protein proliferating cell nuclear antigen (PCNA) and 9-1-1 has been shown in vitro to stimulate steps of the repair process known as long patch base excision repair. Using a system that allows conditional repression of the Rad9 protein in human cell culture, we show that Rad9, and by extension, the 9-1-1 complex, enhances cell survival, is required for efficient exit from G2-phase arrest, and stimulates the repair of damaged DNA following ionizing radiation. These data provide in vivo evidence that the human 9-1-1 complex participates in DNA repair in addition to its previously described role in DNA damage sensing.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, The University of Rochester, NY 14642, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Brandt
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Helt
authors.forename: Peter C
authors.initials: PC
authors.lastname: Keng
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bambara
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005092:Exonucleases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology*; D011839:Radiation, Ionizing; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe; C069930:rad9 protein; D004247:DNA; D005092:Exonucleases; C113574:Rad1 protein, human