Open AccessKin17 facilitates multiple double-strand break repair pathways that govern B cell class switching
Author(s) -
Michael X. Le,
Dania Haddad,
Alexanda K. Ling,
Conglei Li,
Clare C. So,
Amit Chopra,
Rui Hu,
Jaime F. Angulo,
Jason Moffat,
Alberto Martín
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep37215
Subject(s) - cytidine deaminase , homologous recombination , immunoglobulin class switching , gene , dna , double strand , biology , dna repair , genome , genetics , microbiology and biotechnology , computational biology , b cell , antibody
Class switch recombination (CSR) in B cells requires the timely repair of DNA double-stranded breaks (DSBs) that result from lesions produced by activation-induced cytidine deaminase (AID). Through a genome-wide RNAi screen, we identified Kin17 as a gene potentially involved in the maintenance of CSR in murine B cells. In this study, we confirm a critical role for Kin17 in CSR independent of AID activity. Furthermore, we make evident that DSBs generated by AID or ionizing radiation require Kin17 for efficient repair and resolution. Our report shows that reduced Kin17 results in an elevated deletion frequency following AID mutational activity in the switch region. In addition, deficiency in Kin17 affects the functionality of multiple DSB repair pathways, namely homologous recombination, non-homologous end-joining, and alternative end-joining. This report demonstrates the importance of Kin17 as a critical factor that acts prior to the repair phase of DSB repair and is of bona fide importance for CSR.