RAD17

Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene.[5][6]

RAD17
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A1J, 3G65, 3GGR
Identifiers
Aliases	RAD17, CCYC, HR24L, RAD17SP, RAD24, RAD17 checkpoint clamp loader component
External IDs	OMIM: 603139 MGI: 1333807 HomoloGene: 32117 GeneCards: RAD17
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q13.2 Start 69,369,293 bp[1] End 69,414,801 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 D1 Start 100,617,164 bp[2] End 100,651,051 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • GO:0001948 protein binding • ATP binding • chromatin binding • DNA clamp loader activity Cellular component • chromosome, telomeric region • Rad17 RFC-like complex • cell nucleus • nucleoplasm • nucleolus • nuclear chromatin Biological process • mitotic cell cycle checkpoint • DNA replication checkpoint • DNA replication • DNA damage checkpoint • cell cycle • regulation of phosphorylation • negative regulation of DNA replication • cellular response to DNA damage stimulus • mitotic DNA replication checkpoint • DNA repair • regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5884	19356
Ensembl	ENSG00000276618 ENSG00000152942	ENSMUSG00000021635
UniProt	O75943	Q6NXW6
RefSeq (mRNA)	NM_001278622 NM_002873 NM_133338 NM_133339 NM_133340 NM_133341 NM_133342 NM_133343 NM_133344	NM_001044371 NM_001283011 NM_011233
RefSeq (protein)	NP_001265551 NP_002864 NP_579916 NP_579917 NP_579918 NP_579919 NP_579920 NP_579921 NP_579922	NP_001037836 NP_001269940 NP_035363
Location (UCSC)	Chr 5: 69.37 – 69.41 Mb	Chr 13: 100.62 – 100.65 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

Interactions

RAD17 has been shown to interact with:

• Ataxia telangiectasia and Rad3 related,[8][9]
• Ataxia telangiectasia mutated,[8][9]
• HUS1,[10][11]
• NHP2L1,[12]
• POLE,[13]
• RAD1 homolog,[8][10][11] and
• RAD9A.[10][11][14][15]

References

1. ENSG00000152942 GRCh38: Ensembl release 89: ENSG00000276618, ENSG00000152942 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021635 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. PMID 9869296.
6. 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. PMID 9660800.
7. "Entrez Gene: RAD17 RAD17 homolog (S. pombe)".
8. Bao 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. Bibcode:2001Natur.411..969B. doi:10.1038/35082110. PMID 11418864.
9. Kim 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. PMID 10608806.
10. Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A (February 2003). "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. Bibcode:2003PNAS..100.1633B. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958.
11. Rauen 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. PMID 10884395.
12. 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. PMID 10593953.
13. Post SM, Tomkinson AE, Lee EY (October 2003). "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. doi:10.1093/nar/gkg765. PMC 206465. PMID 14500819.
14. Dufault VM, Oestreich AJ, Vroman BT, Karnitz LM (Dec 2003). "Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene". Genomics. 82 (6): 644–51. doi:10.1016/s0888-7543(03)00200-3. PMID 14611806.
15. Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A (September 2001). "Purification and characterization of human DNA damage checkpoint Rad complexes". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11236–41. Bibcode:2001PNAS...9811236L. doi:10.1073/pnas.201373498. PMC 58713. PMID 11572977.

Further reading

• 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. PMID 16354571.
• al-Khodairy F, Carr AM (1992). "DNA repair mutants defining G2 checkpoint pathways in Schizosaccharomyces pombe". EMBO J. 11 (4): 1343–50. doi:10.1002/j.1460-2075.1992.tb05179.x. PMC 556583. PMID 1563350.
• Mossi R, Jónsson ZO, Allen BL, Hardin SH, Hübscher U (1997). "Replication factor C interacts with the C-terminal side of proliferating cell nuclear antigen" (PDF). J. Biol. Chem. 272 (3): 1769–76. doi:10.1074/jbc.272.3.1769. PMID 8999859.
• 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. PMID 9878245.
• 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. PMID 9933569.
• 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. PMID 10208430.
• 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. PMID 10232579.
• 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. PMID 10480350.
• 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. PMID 10593953.
• 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. PMID 10608806.
• 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. PMID 10852904.
• 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. PMID 10884395.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (2001). "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. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• 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. Bibcode:2001Natur.411..969B. doi:10.1038/35082110. PMID 11418864.
• Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A (2001). "Purification and characterization of human DNA damage checkpoint Rad complexes". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11236–41. Bibcode:2001PNAS...9811236L. doi:10.1073/pnas.201373498. PMC 58713. PMID 11572977.
• 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. PMID 11602352.
• Post S, Weng YC, Cimprich K, Chen LB, Xu Y, Lee EY (2001). "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. doi:10.1073/pnas.231364598. PMC 60831. PMID 11687627.