Evolutionary and functional conservation of the DNA non homologous end joining protein, XLF/Cernunnos

Hentges, P., Ahnesorg, P., Pitcher, R. S., Bruce, C. K., Kysela, B., Green, A. J., Bianchi, J., Wilson, T. E., Jackson, S. P. and Doherty, A. J. (2006) Evolutionary and functional conservation of the DNA non homologous end joining protein, XLF/Cernunnos. Journal of Biological Chemistry, 281 (49). pp. 37517-37526. ISSN 0021-9258

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Abstract

Non-homologous end-joining is a major pathway of DNA double-strand break repair in mammalian cells, deficiency in which confers radiosensitivity and immune-deficiency at the whole organism level. A core protein complex comprising the Ku70/80 hetero-dimer together with a complex between DNA ligase IV and XRCC4 is conserved throughout eukaryotes and assembles at double-strand breaks to mediate ligation of broken DNA ends. In Saccharomyces cerevisiae an additional NHEJ protein, Nej1p, physically interacts with the ligase IV complex and is required in vivo for ligation of DNA double-strand breaks. Recent studies with cells derived from radiosensitive and immune-deficient patients have identified the human protein, XLF (also named Cernunnos), as a crucial NHEJ protein. Here we show that XLF and Nej1p are members of the same protein super-family and that this family has members in diverse eukaryotes. Indeed, we show that a member of this family encoded by a previously uncharacterized open-reading frame in the Schizosaccharomyces pombe genome is required for NHEJ in this organism. Furthermore, our data reveal that XLF family proteins can bind to DNA and directly interact with the ligase IV-XRCC4 complex to promote DSB ligation. We therefore conclude that XLF family proteins interact with the ligase IV-XRCC4 complex to constitute the evolutionarily conserved enzymatic core of the NHEJ machinery.

Item Type: Article
Additional Information: Published by the American Society for Biochemistry and Molecular Biology
Subjects: Q Science > QP Physiology
Depositing User: Aidan Doherty
Date Deposited: 13 Nov 2006
Last Modified: 07 Mar 2017 04:38
URI: http://sro.sussex.ac.uk/id/eprint/458
Google Scholar:48 Citations

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