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2017 ; 37
(2
): ä Nephropedia Template TP
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MBD4 Facilitates Immunoglobulin Class Switch Recombination
#MMPMID27777312
Grigera F
; Wuerffel R
; Kenter AL
Mol Cell Biol
2017[Jan]; 37
(2
): ä PMID27777312
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Immunoglobulin heavy chain class switch recombination (CSR) requires targeted
formation of DNA double-strand breaks (DSBs) in repetitive switch region elements
followed by ligation between distal breaks. The introduction of DSBs is initiated
by activation-induced cytidine deaminase (AID) and requires base excision repair
(BER) and mismatch repair (MMR). The BER enzyme methyl-CpG binding domain protein
4 (MBD4) has been linked to the MMR pathway through its interaction with MutL
homologue 1 (MLH1). We find that when Mbd4 exons 6 to 8 are deleted in a
switching B cell line, DSB formation is severely reduced and CSR frequency is
impaired. Impaired CSR can be rescued by ectopic expression of Mbd4 Mbd4
deficiency yields a deficit in DNA end processing similar to that found in MutS
homologue 2 (Msh2)- and Mlh1-deficient B cells. We demonstrate that
microhomology-rich S-S junctions are enriched in cells in which Mbd4 is deleted.
Our studies suggest that Mbd4 is a component of MMR-directed DNA end processing.