The mismatch repair protein Msh6 influences the in vivo AID targeting to the Ig locus.

Journal Article (Journal Article)

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 (Msh6(TD/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, Msh6(TD/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.

Full Text

Duke Authors

Cited Authors

  • Li, Z; Zhao, C; Iglesias-Ussel, MD; Polonskaya, Z; Zhuang, M; Yang, G; Luo, Z; Edelmann, W; Scharff, MD

Published Date

  • April 2006

Published In

Volume / Issue

  • 24 / 4

Start / End Page

  • 393 - 403

PubMed ID

  • 16618598

Pubmed Central ID

  • 16618598

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2006.02.011


  • eng