Biology:RAD17
Generic protein structure example |
Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene.[1][2]
Function
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]
Interactions
RAD17 has been shown to interact with:
- Ataxia telangiectasia and Rad3 related,[4][5]
- Ataxia telangiectasia mutated,[4][5]
- HUS1,[6][7]
- NHP2L1,[8]
- POLE,[9]
- RAD1 homolog,[4][6][7] and
- RAD9A.[6][7][10][11]
References
- ↑ "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. March 1999. PMID 9869296.
- ↑ "Identification of a human homologue of the Schizosaccharomyces pombe rad17+ checkpoint gene". J Biol Chem 273 (29): 18340–6. August 1998. doi:10.1074/jbc.273.29.18340. PMID 9660800.
- ↑ "Entrez Gene: RAD17 RAD17 homolog (S. pombe)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5884.
- ↑ 4.0 4.1 4.2 "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature 411 (6840): 969–74. June 2001. doi:10.1038/35082110. PMID 11418864. Bibcode: 2001Natur.411..969B.
- ↑ 5.0 5.1 "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. Dec 1999. doi:10.1074/jbc.274.53.37538. PMID 10608806.
- ↑ 6.0 6.1 6.2 "Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro". Proc. Natl. Acad. Sci. U.S.A. 100 (4): 1633–8. February 2003. doi:10.1073/pnas.0437927100. PMID 12578958. Bibcode: 2003PNAS..100.1633B.
- ↑ 7.0 7.1 7.2 "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. September 2000. doi:10.1074/jbc.M005782200. PMID 10884395.
- ↑ "HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation". J. Biol. Chem. 274 (51): 36544–9. Dec 1999. doi:10.1074/jbc.274.51.36544. PMID 10593953.
- ↑ "The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon". Nucleic Acids Res. 31 (19): 5568–75. October 2003. doi:10.1093/nar/gkg765. PMID 14500819.
- ↑ "Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene". Genomics 82 (6): 644–51. Dec 2003. doi:10.1016/s0888-7543(03)00200-3. PMID 14611806.
- ↑ "Purification and characterization of human DNA damage checkpoint Rad complexes". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11236–41. September 2001. doi:10.1073/pnas.201373498. PMID 11572977. Bibcode: 2001PNAS...9811236L.
Further reading
- "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–34. 2006. doi:10.1038/sj.cr.7290370. PMID 16354571.
- "DNA repair mutants defining G2 checkpoint pathways in Schizosaccharomyces pombe". EMBO J. 11 (4): 1343–50. 1992. doi:10.1002/j.1460-2075.1992.tb05179.x. PMID 1563350.
- "Replication factor C interacts with the C-terminal side of proliferating cell nuclear antigen". J. Biol. Chem. 272 (3): 1769–76. 1997. doi:10.1074/jbc.272.3.1769. PMID 8999859. http://www.zora.uzh.ch/825/1/Mossi_replication.pdf.
- "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. 1999. doi:10.1006/geno.1998.5587. PMID 9878245.
- "Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene". Genomics 55 (2): 219–28. 1999. doi:10.1006/geno.1998.5642. PMID 9933569.
- "hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle checkpoint gene, stimulates p53 accumulation". Oncogene 18 (9): 1689–99. 1999. doi:10.1038/sj.onc.1202469. PMID 10208430.
- "HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma". Cancer Res. 59 (9): 2023–8. 1999. PMID 10232579.
- "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. 1999. doi:10.1007/s004390051058. PMID 10480350.
- "HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation". J. Biol. Chem. 274 (51): 36544–9. 2000. doi:10.1074/jbc.274.51.36544. PMID 10593953.
- "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. 2000. doi:10.1074/jbc.274.53.37538. PMID 10608806.
- "Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage". J. Biol. Chem. 275 (34): 26343–8. 2000. doi:10.1074/jbc.M001244200. PMID 10852904.
- "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. 2000. doi:10.1074/jbc.M005782200. PMID 10884395.
- "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863.
- "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature 411 (6840): 969–74. 2001. doi:10.1038/35082110. PMID 11418864. Bibcode: 2001Natur.411..969B.
- "Purification and characterization of human DNA damage checkpoint Rad complexes". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11236–41. 2001. doi:10.1073/pnas.201373498. PMID 11572977. Bibcode: 2001PNAS...9811236L.
- "Multiple alternative splicing forms of human RAD17 and their differential response to ionizing radiation". Gene 277 (1–2): 145–52. 2001. doi:10.1016/S0378-1119(01)00692-8. PMID 11602352.
- "Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G1/S checkpoint activation in response to DNA damage". Proc. Natl. Acad. Sci. U.S.A. 98 (23): 13102–7. 2001. doi:10.1073/pnas.231364598. PMID 11687627. Bibcode: 2001PNAS...9813102P.