The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by ATR after the damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Eight alternatively spliced transcript variants of this gene, which encode four distinct proteins, have been reported.[3]
↑Bao S, Shen X, Shen K, Liu Y, Wang XF (March 1999). "The mammalian Rad24 homologous to yeast Saccharomyces cerevisiae Rad24 and Schizosaccharomyces pombe Rad17 is involved in DNA damage checkpoint". Cell Growth Differ. 9 (12): 961–7. PMID9869296.
↑Parker AE, Van de Weyer I, Laus MC, Verhasselt P, Luyten WH (August 1998). "Identification of a human homologue of the Schizosaccharomyces pombe rad17+ checkpoint gene". J Biol Chem. 273 (29): 18340–6. doi:10.1074/jbc.273.29.18340. PMID9660800.
↑ 4.04.14.2Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, Abraham RT, Wang XF (June 2001). "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature. 411 (6840): 969–74. doi:10.1038/35082110. PMID11418864.
↑ 5.05.1Kim ST, Lim DS, Canman CE, Kastan MB (Dec 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID10608806.
↑ 7.07.17.2Rauen M, Burtelow MA, Dufault VM, Karnitz LM (September 2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. doi:10.1074/jbc.M005782200. PMID10884395.
↑Chang MS, Sasaki H, Campbell MS, Kraeft SK, Sutherland R, Yang CY, Liu Y, Auclair D, Hao L, Sonoda H, Ferland LH, Chen LB (Dec 1999). "HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation". J. Biol. Chem. 274 (51): 36544–9. doi:10.1074/jbc.274.51.36544. PMID10593953.
Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–34. doi:10.1038/sj.cr.7290370. PMID16354571.
Dean FB, Lian L, O'Donnell M (1999). "cDNA cloning and gene mapping of human homologs for Schizosaccharomyces pombe rad17, rad1, and hus1 and cloning of homologs from mouse, Caenorhabditis elegans, and Drosophila melanogaster". Genomics. 54 (3): 424–36. doi:10.1006/geno.1998.5587. PMID9878245.
Bluyssen HA, Naus NC, van Os RI, Jaspers I, Hoeijmakers JH, de Klein A (1999). "Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene". Genomics. 55 (2): 219–28. doi:10.1006/geno.1998.5642. PMID9933569.
Li L, Peterson CA, Kanter-Smoler G, Wei YF, Ramagli LS, Sunnerhagen P, Siciliano MJ, Legerski RJ (1999). "hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle checkpoint gene, stimulates p53 accumulation". Oncogene. 18 (9): 1689–99. doi:10.1038/sj.onc.1202469. PMID10208430.
Bao S, Chang MS, Auclair D, Sun Y, Wang Y, Wong WK, Zhang J, Liu Y, Qian X, Sutherland R, Magi-Galluzi C, Weisberg E, Cheng EY, Hao L, Sasaki H, Campbell MS, Kraeft SK, Loda M, Lo KM, Chen LB (1999). "HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma". Cancer Res. 59 (9): 2023–8. PMID10232579.
von Deimling F, Scharf JM, Liehr T, Rothe M, Kelter AR, Albers P, Dietrich WF, Kunkel LM, Wernert N, Wirth B (1999). "Human and mouse RAD17 genes: identification, localization, genomic structure and histological expression pattern in normal testis and seminoma". Hum. Genet. 105 (1–2): 17–27. doi:10.1007/s004390051058. PMID10480350.
Chang MS, Sasaki H, Campbell MS, Kraeft SK, Sutherland R, Yang CY, Liu Y, Auclair D, Hao L, Sonoda H, Ferland LH, Chen LB (2000). "HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation". J. Biol. Chem. 274 (51): 36544–9. doi:10.1074/jbc.274.51.36544. PMID10593953.
Kim ST, Lim DS, Canman CE, Kastan MB (2000). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID10608806.
Burtelow MA, Kaufmann SH, Karnitz LM (2000). "Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage". J. Biol. Chem. 275 (34): 26343–8. doi:10.1074/jbc.M001244200. PMID10852904.
Rauen M, Burtelow MA, Dufault VM, Karnitz LM (2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. doi:10.1074/jbc.M005782200. PMID10884395.
Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, Abraham RT, Wang XF (2001). "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature. 411 (6840): 969–74. doi:10.1038/35082110. PMID11418864.
Chen MS, Higashikubo R, Laszlo A, Roti Roti J (2001). "Multiple alternative splicing forms of human RAD17 and their differential response to ionizing radiation". Gene. 277 (1–2): 145–52. doi:10.1016/S0378-1119(01)00692-8. PMID11602352.