Combined deficiency of MSH2 and Sμ region abolishes class switch recombination

Claire Leduc, Dania Haddad, Nathalie Laviolette-Malirat, Ngoc Sa Nguyen Huu, Ahmed Amine Khamlichi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Class switch recombination (CSR) is mediated by G-rich tandem repeated sequences termed switch regions. Transcription of switch regions generates single-stranded R loops that provide substrates for activation-induced cytidine deaminase. Mice deficient in MSH2 have a mild defect in CSR and analysis of their switch junctions has led to amodel inwhichMSH2 is more critical for switch recombination events outside than within the tandem repeats. It is also known that deletion of the whole Sμ region severely impairs but does not abrogate CSR despite the lack of detectable R loops. Here, we demonstrate that deficiency of both MSH2 and the Sμ region completely abolishes CSR and that the abrogation occurs at the genomic level. This finding further supports the crucial role of MSH2 outside the tandem repeats. It also indicates that during CSR, MSH2 has access to activation-induced cytidine deaminase targets in R-loop-deficient Iμ-Cμ sequences rarely used in CSR, suggesting an MSH2-dependent DNA processing activity at the Il exon that may decrease with transcription elongation across the Sμ region.

Original languageEnglish
Pages (from-to)2925-2931
Number of pages7
JournalEuropean Journal of Immunology
Volume40
Issue number10
DOIs
Publication statusPublished - 1 Oct 2010

Keywords

  • Class switching
  • Germ-line transcription
  • Mismatch repair
  • Tandem repeats

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