Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation Journal Article

   

Authors:	Simsek, D.; Jasin, M.
Article Title:	Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation
Abstract:	Chromosomal translocations in hematologic and mesenchymal tumors form overwhelmingly by nonhomologous end-joining (NHEJ). Canonical NHEJ, essential for the repair of radiation-induced and some programmed double-strand breaks (DSBs), requires the Xrcc4-ligase IV complex. For other DSBs, the requirement for Xrcc4-ligase IV is less stringent, suggesting the existence of alternative end-joining (alt-NHEJ) pathways. To understand the contributions of the canonical NHEJ and alt-NHEJ pathways, we examined translocation formation in cells deficient in Xrcc4-ligase IV. We found that Xrcc4-ligase IV is not required for but rather suppresses translocations. Translocation breakpoint junctions have similar characteristics in wild-type cells and cells deficient in Xrcc4-ligase IV, including an unchanged bias toward microhomology, unlike what is observed for intrachromosomal DSB repair. Complex insertions in some junctions show that joining can be iterative, encompassing successive processing steps before joining. Our results imply that alt-NHEJ is the primary mediator of translocation formation in mammalian cells. © 2010 Nature America, Inc. All rights reserved.
Keywords:	controlled study; unclassified drug; dna-binding proteins; nonhuman; animal cell; mouse; mammalia; dna repair; wild type; chromosome translocation; double stranded dna break; translocation, genetic; xrcc4 protein; gene insertion; polydeoxyribonucleotide synthase; mutant; dna ligases; polydeoxyribonucleotide synthase iv; alternative non homologous end joining; canonical non homologous end joining
Journal Title:	Nature Structural and Molecular Biology
Volume:	17
Issue:	4
ISSN:	1545-9993
Publisher:	Nature Publishing Group
Date Published:	2010-04-01
Start Page:	410
End Page:	416
Language:	English
DOI:	10.1038/nsmb.1773
PUBMED:	20208544
PROVIDER:	scopus
PMCID:	PMC3893185
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77950462986&partnerID=40&md5=f1a35d3de2f9e8517f2128457799bb0d
Notes:	--- - "Cited By (since 1996): 14" - "Export Date: 20 April 2011" - "CODEN: NSMBC" - "Source: Scopus"

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