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

Immunity
Ziqiang LiMatthew D Scharff

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 (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.

References

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Citations

Oct 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sergio RoaMatthew D Scharff
Dec 28, 2006·The Journal of Experimental Medicine·Frédéric DelbosClaude-Agnès Reynaud
Jul 15, 2009·Molecular and Cellular Biology·Darina FriederAlberto Martin
Jan 1, 2016·DNA Repair·Kimberly J Zanotti, Patricia J Gearhart
Jun 19, 2012·Seminars in Immunology·Richard ChahwanSergio Roa
Nov 22, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Richard ChahwanSergio Roa
Feb 26, 2011·Developmental and Comparative Immunology·Vasco M Barreto, Brad G Magor
Jul 7, 2009·Trends in Microbiology·James C HuDeborah A Siegele
Oct 28, 2008·DNA Repair·Thomas MaccarthyAviv Bergman
Dec 18, 2007·European Journal of Immunology·Palash BhattacharyaAmy L Kenter
Jul 25, 2006·Trends in Molecular Medicine·Virginia G de Yébenes, Almudena R Ramiro
Jun 2, 2006·Trends in Immunology·Paolo CasaliHong Zan
Apr 18, 2006·Current Opinion in Immunology·Stella A Martomo, Patricia J Gearhart
Feb 29, 2008·Annual Review of Immunology·Jonathan U PeledMatthew D Scharff
Nov 30, 2006·DNA Repair·Irina V Kovtun, Cynthia T McMurray
Nov 9, 2006·The Journal of Biological Chemistry·Nasim A BegumTasuku Honjo
May 9, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohammed Mansour Abbas EidNobuo Sakaguchi
Jan 1, 2017·Nucleic Acids Research·Eddy Sanchai ThientosapolChristopher J Jolly
Aug 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sanjay RanjitJanet Stavnezer
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong Ming ShenUrsula Storb
Feb 22, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabrina A VolpiBarbara K Birshtein
Dec 8, 2021·Proceedings of the National Academy of Sciences of the United States of America·Guojun YuMatthew D Scharff

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