The Mismatch Repair Protein Msh6 Influences the In Vivo AID Targeting to the Ig Locus

Ziqiang Li, Chunfang Zhao, Maria D. Iglesias-Ussel, Zhanna Polonskaya, Min Zhuang, Guozhe Yang, Zhonghui Luo, Winfried Edelmann, Matthew D. Scharff

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID), which preferentially deaminates deoxycytidines at WRC (W = A/T, R = A/G) motifs in vitro. The mechanisms responsible for targeting AID and for organizing the queue of enzymes involved in vivo have been elusive. Here, we examined point mutant knockin Msh6 mice (Msh6TD/TD), which lack the second phase of SHM but retain all the proteins involved, and found that AID was frequently targeted to non-WRC motifs. Unexpectedly, by comparing SHM and CSR in wild-type, Msh6TD/TD, and age-matched Msh6-/- mice, we discovered that the presence of Msh6 protein influenced the AID targeting in phase one of SHM and mediated the proper targeting of recombination sites in CSR in vivo. Our data suggest that Msh6 plays a scaffolding role in the first phase of SHM, in addition to its enzymatic role in the second phase of SHM.

Original languageEnglish (US)
Pages (from-to)393-403
Number of pages11
JournalImmunity
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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