Title
Mismatch repair converts AID-instigated nicks to double-strand breaks for antibody class-switch recombination
UMMS Affiliation
Department of Molecular Genetics and Microbiology
Date
November 2005
Document Type
Article
Subjects
Animals; B-Lymphocytes; *Base Pair Mismatch; Cytidine Deaminase; *DNA Repair; Humans; *Immunoglobulin Class Switching; Mice; Models, Genetic; Recombination, Genetic
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.
Rights and Permissions
Citation: Trends Genet. 2006 Jan;22(1):23-8. Epub 2005 Nov 23. Link to article on publisher's site
Related Resources
PubMed ID
16309779
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