An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway Journal Article
| Authors: | Zhang, Y.; Jasin, M. |
| Article Title: | An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway |
| 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. © 2011 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; gene deletion; nonhuman; animal cell; mouse; transcription factor; wild type; dna; chromosome breakage; chromosome translocation; ku antigen; transcription factor ctip |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 18 |
| Issue: | 1 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-01-01 |
| Start Page: | 80 |
| End Page: | 85 |
| Language: | English |
| DOI: | 10.1038/nsmb.1940 |
| PROVIDER: | scopus |
| PMCID: | PMC3261752 |
| PUBMED: | 21131978 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 4 March 2011" - "CODEN: NSMBC" - "Source: Scopus" |
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