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RAD17

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RAD17
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRAD17, CCYC, HR24L, RAD17SP, RAD24, RAD17 checkpoint clamp loader component
External IDsOMIM: 603139; MGI: 1333807; HomoloGene: 32117; GeneCards: RAD17; OMA:RAD17 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5884

19356

Ensembl

ENSG00000276618
ENSG00000152942

ENSMUSG00000021635

UniProt

O75943

Q6NXW6

RefSeq (mRNA)

NM_001044371
NM_001283011
NM_011233

RefSeq (protein)

NP_001037836
NP_001269940
NP_035363

Location (UCSC)Chr 5: 69.37 – 69.41 MbChr 13: 100.75 – 100.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

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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]

Meiosis

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During meiosis in yeast and in mammals, RAD17 protein functions as a DNA damage sensor promoting DNA checkpoint control.[8] In yeast, the RAD17 protein facilitates proper assembly of the meiotic crossover recombination complex containing the RAD51 protein, thus promoting efficient repair of meiotic DNA double-strand breaks.[9] During male meiosis in maize (Zea mays), the ZmRAD17 gene is involved in repair of DNA double strand breaks, likely by promoting synaptonemal complex assembly.[8]

Interactions

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RAD17 has been shown to interact with:

References

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  1. ^ a b c ENSG00000152942 GRCh38: Ensembl release 89: ENSG00000276618, ENSG00000152942 – Ensembl, May 2017
  2. ^ a b c 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 (December 1998). "The mammalian Rad24 homologous to yeast Saccharomyces cerevisiae Rad24 and Schizosaccharomyces pombe Rad17 is involved in DNA damage checkpoint". Cell Growth & Differentiation. 9 (12): 961–967. PMID 9869296.
  6. ^ Parker AE, Van de Weyer I, Laus MC, Verhasselt P, Luyten WH (July 1998). "Identification of a human homologue of the Schizosaccharomyces pombe rad17+ checkpoint gene". The Journal of Biological Chemistry. 273 (29): 18340–18346. doi:10.1074/jbc.273.29.18340. PMID 9660800.
  7. ^ "Entrez Gene: RAD17 RAD17 homolog (S. pombe)".
  8. ^ a b Zhang T, Jing JL, Liu L, He Y (2021). "ZmRAD17 Is Required for Accurate Double-Strand Break Repair During Maize Male Meiosis". Frontiers in Plant Science. 12: 626528. doi:10.3389/fpls.2021.626528. PMC 7952653. PMID 33719299.
  9. ^ Shinohara M, Sakai K, Ogawa T, Shinohara A (July 2003). "The mitotic DNA damage checkpoint proteins Rad17 and Rad24 are required for repair of double-strand breaks during meiosis in yeast". Genetics. 164 (3): 855–865. doi:10.1093/genetics/164.3.855. PMC 1462628. PMID 12871899.
  10. ^ a b c Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, et al. (June 2001). "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature. 411 (6840): 969–974. Bibcode:2001Natur.411..969B. doi:10.1038/35082110. PMID 11418864. S2CID 4429058.
  11. ^ a b Kim ST, Lim DS, Canman CE, Kastan MB (December 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". The Journal of Biological Chemistry. 274 (53): 37538–37543. doi:10.1074/jbc.274.53.37538. PMID 10608806.
  12. ^ a b c 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". Proceedings of the National Academy of Sciences of the United States of America. 100 (4): 1633–1638. Bibcode:2003PNAS..100.1633B. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958.
  13. ^ a b c 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". The Journal of Biological Chemistry. 275 (38): 29767–29771. doi:10.1074/jbc.M005782200. PMID 10884395.
  14. ^ Chang MS, Sasaki H, Campbell MS, Kraeft SK, Sutherland R, Yang CY, et al. (December 1999). "HRad17 colocalizes with NHP2L1 in the nucleolus and redistributes after UV irradiation". The Journal of Biological Chemistry. 274 (51): 36544–36549. doi:10.1074/jbc.274.51.36544. PMID 10593953.
  15. ^ 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 Research. 31 (19): 5568–5575. doi:10.1093/nar/gkg765. PMC 206465. PMID 14500819.
  16. ^ Dufault VM, Oestreich AJ, Vroman BT, Karnitz LM (December 2003). "Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene". Genomics. 82 (6): 644–651. doi:10.1016/s0888-7543(03)00200-3. PMID 14611806.
  17. ^ Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A (September 2001). "Purification and characterization of human DNA damage checkpoint Rad complexes". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11236–11241. Bibcode:2001PNAS...9811236L. doi:10.1073/pnas.201373498. PMC 58713. PMID 11572977.

Further reading

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