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10.1128/MCB.00316-16

http://scihub22266oqcxt.onion/10.1128/MCB.00316-16
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C5214850!5214850 !27777312
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suck abstract from ncbi


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pmid27777312
      Mol+Cell+Biol 2017 ; 37 (2 ): ä
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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 show ga
  • 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.
  • |Animals [MESH]
  • |Base Sequence [MESH]
  • |CRISPR-Cas Systems/genetics [MESH]
  • |Cell Line [MESH]
  • |DNA Breaks, Double-Stranded [MESH]
  • |Endodeoxyribonucleases/deficiency/*metabolism [MESH]
  • |Exons/genetics [MESH]
  • |Gene Deletion [MESH]
  • |Gene Expression Regulation [MESH]
  • |Genes, Dominant [MESH]
  • |Genetic Complementation Test [MESH]
  • |Immunoglobulin Class Switching/*genetics [MESH]
  • |Mice, Knockout [MESH]
  • |Protein Isoforms/metabolism [MESH]


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