title: Kin17 facilitates multiple double-strand break repair pathways that govern B cell class switching.
abstract: 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.
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Michael X
authors.initials: MX
authors.lastname: Le
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Dania
authors.initials: D
authors.lastname: Haddad
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Alexanda K
authors.initials: AK
authors.lastname: Ling
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Conglei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Clare C
authors.initials: CC
authors.lastname: So
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Chopra
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.affiliation: Laboratoire de Radio Toxicologie, CEA, Université Paris-Saclay, Arpajon, 91297, France.
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Angulo
authors.affiliation: Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Moffat
authors.affiliation: Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S1A8, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martin
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C489487:KIN protein, human; D016601:RNA-Binding Proteins