A critical role for REV1 in regulating the induction of C:G transitions and A:T mutations during Ig gene hypermutation

Keiji Masuda, Rika Ouchida, Yingqian Li, Xiang Gao, Hiromi Mori, Ji Yang Wang

研究成果: Contribution to journalArticle査読

32 被引用数 (Scopus)

抄録

REV1 is a deoxycytidyl transferase that catalyzes the incorporation of deoxycytidines opposite deoxyguanines and abasic sites. To explore the role of its catalytic activity in Ig gene hypermutation in mammalian cells, we have generated mice expressing a catalytically inactive REV1 (REV1AA). REV1AA mice developed normally and were fertile on a pure C57BL/6 genetic background. B and T cell development and maturation were not affected, and REV1AA B cells underwent normal activation and class switch recombination. Analysis of Ig gene hypermutation in REV1AA mice revealed a great decrease of C to G and G to C transversions, consistent with the disruption of its deoxycytidyl transferase activity. Intriguingly, REV1AA mice also exhibited a significant reduction of C to T and G to A transitions. Moreover, each type of nucleotide substitutions at A:T base pairs was uniformly reduced in REV1AA mice, a phenotype similar to that observed in mice haploinsufficient for Polh. These results reveal an unexpected role for REV1 in the generation of C:G transitions and A:T mutations and suggest that REV1 is involved in multiple mutagenic pathways through functional interaction with other polymerases during the hypermutation process.

本文言語英語
ページ(範囲)1846-1850
ページ数5
ジャーナルJournal of Immunology
183
3
DOI
出版ステータス出版済み - 8 1 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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