title: Mismatch repair converts AID-instigated nicks to double-strand breaks for antibody class-switch recombination.
abstract: Mismatch repair (MMR) proteins are important for antibody class-switch recombination (CSR), but their roles are unknown. We propose a model for the function of MMR in CSR in which MMR proteins convert single-strand nicks instigated by activation-induced cytidine deaminase (AID) into the double-strand breaks (DSBs) that are required for CSR. This model does not invoke any novel functions for MMR but simply posits that, owing to numerous single-strand nicks in the switch (S) regions of both DNA strands, when MMR proteins are recruited by U:G mismatches, they excise one strand of DNA and soon reach a nick on the opposite strand. This halts excision activity and creates a DSB. This model explains why B cells that lack either S mu and MSH2 or UNG and MSH2 cannot undergo CSR.
authors.affiliation: Department of Molecular Genetics and Microbiology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655-0122, USA. janet.stavnezer@umassmed.edu
authors.forename: Janet
authors.initials: J
authors.lastname: Stavnezer
authors.forename: Carol E
authors.initials: CE
authors.lastname: Schrader
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020137:Base Pair Mismatch; D003564:Cytidine Deaminase / Q000378:metabolism; D004260:DNA Repair; D006801:Humans; D017578:Immunoglobulin Class Switching; D051379:Mice; D008957:Models, Genetic; D011995:Recombination, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase