DNA repair protein XRCC4

XRCC4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesXRCC4, SSMED, X-ray repair complementing defective repair in Chinese hamster cells 4, X-ray repair cross complementing 4, hXRCC4
External IDsOMIM: 194363; MGI: 1333799; HomoloGene: 2555; GeneCards: XRCC4; OMA:XRCC4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

7518

108138

Ensembl

ENSG00000152422

ENSMUSG00000021615

UniProt

Q13426

Q924T3

RefSeq (mRNA)

NM_003401
NM_022406
NM_022550
NM_001318012
NM_001318013

NM_028012

RefSeq (protein)

NP_082288

Location (UCSC)Chr 5: 83.08 – 83.35 MbChr 13: 89.92 – 90.24 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DNA repair protein XRCC4 (hXRCC4) also known as X-ray repair cross-complementing protein 4 is a protein that in humans is encoded by the XRCC4 gene. XRCC4 is also expressed in many other animals, fungi and plants.[5] hXRCC4 is one of several core proteins involved in the non-homologous end joining (NHEJ) pathway to repair DNA double strand breaks (DSBs).[6][7][8]

NHEJ requires two main components to achieve successful completion. The first component is the cooperative binding and phosphorylation of artemis by the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). Artemis cleaves the ends of damaged DNA to prepare it for ligation. The second component involves the bridging of DNA to DNA ligase 4, by hXRCC4, with the aid of Cernunnos-XLF. DNA-PKcs and hXRCC4 are anchored to Ku70 / Ku80 heterodimer, which are bound to the DNA ends.[9]

Since hXRCC4 is the key protein that enables interaction of DNA ligase 4 to damaged DNA and therefore ligation of the ends, mutations in the XRCC4 gene were found to cause embryonic lethality in mice and developmental inhibition and immunodeficiency in humans.[9] Furthermore, certain mutations in XRCC4 are associated with an increased risk of cancer.[10]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000152422 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021615 – 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. ^ West CE, Waterworth WM, Jiang Q, Bray CM (October 2000). "Arabidopsis DNA ligase IV is induced by gamma-irradiation and interacts with an Arabidopsis homologue of the double strand break repair protein XRCC4". Plant J. 24 (1): 67–78. doi:10.1046/j.1365-313x.2000.00856.x. PMID 11029705.
  6. ^ Oksenych V, Kumar V, Liu X, Guo C, Schwer B, Zha S, Alt FW (February 2013). "Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining". Proc. Natl. Acad. Sci. U.S.A. 110 (6): 2234–9. Bibcode:2013PNAS..110.2234O. doi:10.1073/pnas.1222573110. PMC 3568359. PMID 23345432.
  7. ^ Yurchenko V, Xue Z, Sadofsky MJ (March 2006). "SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair". Mol. Cell. Biol. 26 (5): 1786–94. doi:10.1128/MCB.26.5.1786-1794.2006. PMC 1430232. PMID 16478998.
  8. ^ Watson J (2008). Molecular Biology of the Gene. New York: Cold Spring Harbor Laboratory Press. pp. 148, 265–278. ISBN 978-0-8053-9592-1.
  9. ^ a b Andres SN, Vergnes A, Ristic D, Wyman C, Modesti M, Junop M (February 2012). "A human XRCC4-XLF complex bridges DNA". Nucleic Acids Res. 40 (4): 1868–78. doi:10.1093/nar/gks022. PMC 3287209. PMID 22287571.
  10. ^ Shao N, Jiang WY, Qiao D, Zhang SG, Wu Y, Zhang XX, Hua LX, Ding Y, Feng NH (2012). "An updated meta-analysis of XRCC4 polymorphisms and cancer risk based on 31 case-control studies". Cancer Biomark. 12 (1): 37–47. doi:10.3233/CBM-120292. PMID 23321468.