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Cell Death Differ. 2015 Jun;22(6):890-7. doi: 10.1038/cdd.2015.22. Epub 2015 Mar 13.

XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair.

Author information

1
MRC Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, UK.

Abstract

Repair of double-stranded DNA breaks (DSBs) in mammalian cells primarily occurs by the non-homologous end-joining (NHEJ) pathway, which requires seven core proteins (Ku70/Ku86, DNA-PKcs (DNA-dependent protein kinase catalytic subunit), Artemis, XRCC4-like factor (XLF), XRCC4 and DNA ligase IV). Here we show using combined affinity purification and mass spectrometry that DNA-PKcs co-purifies with all known core NHEJ factors. Furthermore, we have identified a novel evolutionary conserved protein associated with DNA-PKcs-c9orf142. Computer-based modelling of c9orf142 predicted a structure very similar to XRCC4, hence we have named c9orf142-XLS (XRCC4-like small protein). Depletion of c9orf142/XLS in cells impaired DSB repair consistent with a defect in NHEJ. Furthermore, c9orf142/XLS interacted with other core NHEJ factors. These results demonstrate the existence of a new component of the NHEJ DNA repair pathway in mammalian cells.

PMID:
25941166
PMCID:
PMC4423191
DOI:
10.1038/cdd.2015.22
[Indexed for MEDLINE]
Free PMC Article

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