The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation.
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.
Brandt
Patrick D
PD
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, The University of Rochester, NY 14642, USA.
Helt
Christopher E
CE
Keng
Peter C
PC
Bambara
Robert A
RA
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
D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe; C069930:rad9 protein; D004247:DNA; D005092:Exonucleases; C113574:Rad1 protein, human