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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review: 

Xrcc4  -  X-ray repair complementing defective...

Mus musculus

Synonyms: 2310057B22Rik, AW413319, AW545101, DNA repair protein XRCC4, X-ray repair cross-complementing protein 4
 
 
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Disease relevance of Xrcc4

  • Interestingly, Xrcc4(-/-)p53S18/23A mice fail to develop tumors like the pro-B cell lymphomas uniformly developed in Xrcc4(-/-) p53(-/-) animals, but exhibit developmental defects typical of accelerated ageing [1].
 

High impact information on Xrcc4

  • In addition, p53S18/23A, but not p53S18A, could completely rescue embryonic lethality of Xrcc4(-/-) mice that is caused by massive p53-dependent neuronal apoptosis [1].
  • In the first step, few double-strand breaks (DSBs) are produced, recombination is slightly increased, but cell lines defective in non-homologous end-joining (NHEJ) affected in ku86 (xrs6) or xrcc4 (XR-1) genes show enhanced sensitivity to replication inhibitors [2].
  • The C-terminal stalk comprising a single alpha-helix >120 A in length is partly incorporated into a four-helix bundle in the Xrcc4 tetramer and partly involved in interacting with ligase IV [3].
  • Crystal structure of the Xrcc4 DNA repair protein and implications for end joining [3].
  • Transfection of M10 cells with the murine Xrcc4 cDNA completely rescued X-ray sensitivity of the mutant cells [4].
 

Anatomical context of Xrcc4

 

Associations of Xrcc4 with chemical compounds

  • In the present study, sequence analysis of Xrcc4 cDNA in M10 cells disclosed a transversion of A (370) to T, which results in a change of arginine (124) to a termination codon [4].
  • A sequence analysis of Xrcc4 cDNA in LX830 cells disclosed a transition of G to A at nucleotide position 129, which resulted in a change of tryptophan (43) to a termination codon [5].
 

Other interactions of Xrcc4

  • The Xrcc4 structure suggests a possible mode of coupling ligase IV association with DNA binding for effective ligation of DNA ends [3].
 

Analytical, diagnostic and therapeutic context of Xrcc4

  • Complementation tests between LX830 cells and radiation-sensitive mutants of M10 (Xrcc4 deficient cells) or SX10 (DNA ligase IV deficient cells) cells showed that M10 cells did not complement LX830 cells, but SX10 cells did, suggesting that LX830 cells would belong to the X-ray-cross complementation group (XRCC4) [5].

References

  1. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. Chao, C., Herr, D., Chun, J., Xu, Y. EMBO J. (2006) [Pubmed]
  2. Characterization of homologous recombination induced by replication inhibition in mammalian cells. Saintigny, Y., Delacôte, F., Varès, G., Petitot, F., Lambert, S., Averbeck, D., Lopez, B.S. EMBO J. (2001) [Pubmed]
  3. Crystal structure of the Xrcc4 DNA repair protein and implications for end joining. Junop, M.S., Modesti, M., Guarné, A., Ghirlando, R., Gellert, M., Yang, W. EMBO J. (2000) [Pubmed]
  4. Molecular characterization of ionizing radiation-hypersensitive mutant M10 cells. Mori, M., Itsukaichi, H., Nakamura, A., Sato, K. Mutat. Res. (2001) [Pubmed]
  5. Identification of a new G-to-A transition mutation at nucleotide position 129 of the Xrcc4 gene in ionizing radiation-hypersensitive mutant LX830 cells. Itsukaichi, H., Mori, M., Nakamura, A., Sato, K. J. Radiat. Res. (2003) [Pubmed]
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