We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway.
- Authors
Zhang, Yu; Jasin, Maria
- Abstract
Chromosomal translocations arise from the misjoining of DNA breaks, but the identity of the DNA repair factors and activities involved in their formation has been elusive. Here we show that depletion of CtIP, a DNA end-resection factor, results in a substantial decrease in chromosomal translocation frequency in mouse cells. Moreover, microhomology usage, a signature of the alternative nonhomologous end-joining pathway (alt-NHEJ), is significantly lower in translocation breakpoint junctions recovered from CtIP-depleted cells than in those from wild-type cells. Thus, we directly demonstrate that CtIP-mediated alt-NHEJ has a primary role in translocation formation. CtIP depletion in Ku70(-/-) cells reduces translocation frequency without affecting microhomology, indicating that Ku70-dependent NHEJ generates a fraction of translocations in wild-type cells. Translocations from both wild-type and Ku70(-/-) cells have smaller deletions on the participating chromosomes when CtIP is depleted, implicating the end-resection activity of CtIP in translocation formation.
- Publication
Nature structural & molecular biology, 2011, Vol 18, Issue 1, p80
- ISSN
1545-9985
- Publication type
Journal Article
- DOI
10.1038/nsmb.1940