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 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 4 March 2011" - "CODEN: NSMBC" - "Source: Scopus" |
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