First Author | Grigera F | Year | 2017 |
Journal | Mol Cell Biol | Volume | 37 |
Issue | 2 | PubMed ID | 27777312 |
Mgi Jnum | J:244355 | Mgi Id | MGI:5913134 |
Doi | 10.1128/MCB.00316-16 | Citation | Grigera F, et al. (2017) MBD4 Facilitates Immunoglobulin Class Switch Recombination. Mol Cell Biol 37(2) |
abstractText | 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. |