CtIP promotes microhomology-mediated alternative end joining during class-switch recombination Journal Article

Authors: Lee Theilen, M.; Matthews, A. J.; Kelly, D.; Zheng, S.; Chaudhuri, J.
Article Title: CtIP promotes microhomology-mediated alternative end joining during class-switch recombination
Abstract: Immunoglobulin heavy chain (Igh locus) class-switch recombination (CSR) requires targeted introduction of DNA double strand breaks (DSBs) into repetitive 'switch'-region DNA elements in the Igh locus and subsequent ligation between distal DSBs. Both canonical nonhomologous end joining (C-NHEJ) that seals DNA ends with little or no homology and a poorly defined alternative end joining (A-NHEJ, also known as alt-NHEJ) process that requires microhomology ends for ligation have been implicated in CSR. Here, we show that the DNA end-processing factor CtIP is required for microhomology-directed A-NHEJ during CSR. Additionally, we demonstrate that microhomology joins that are enriched upon depletion of the C-NHEJ component Ku70 require CtIP. Finally, we show that CtIP binds to switch-region DNA in a fashion dependent on activation-induced cytidine deaminase. Our results establish CtIP as a bona fide component of microhomology-dependent A-NHEJ and unmask a hitherto unrecognized physiological role of microhomology-mediated end joining in a C-NHEJ-proficient environment. © 2011 Nature America, Inc. All rights reserved.
Keywords: controlled study; nonhuman; animal cell; mouse; homologous recombination; carboxy terminal sequence; protein binding; activation induced cytidine deaminase; dna; gene rearrangement; immunoglobulin gene; cytidine deaminase; ku antigen
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: 75
End Page: 80
Language: English
DOI: 10.1038/nsmb.1942
PROVIDER: scopus
PUBMED: 21131982
PMCID: PMC3471154
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 4 March 2011" - "CODEN: NSMBC" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Mieun Lee
    3 Lee
  2. Dierdre Brittany Kelly
    1 Kelly