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ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells.

ABSTRACT: Somatic mutations accumulate in senescent cells. Bcl6, which functions as a transcriptional repressor, has been identified as a potent inhibitor of cell senescence, but a role of Bcl6 in the accumulation of somatic mutations has remained unclear. Ig class-switch recombination simultaneously induces somatic mutations in an IgM class-switch (Ig-S?) region of IgG B cells. Surprisingly, mutations were detected in the Ig-S? region of Bcl6-deficient IgM B cells without class-switch recombination, and these mutations were mainly generated by conversion of adenosine to guanosine, suggesting a novel DNA mutator in the B cells. The ADAR1 (adenosine deaminase acting on RNA1) gene was overexpressed in Bcl6-deficient cells, and its promoter analysis revealed that ADAR1 is a molecular target of Bcl6. Exogenous ADAR1 induced adenosine-targeted DNA mutations in IgM B cells from ADAR1-transgenic mice and in wild-type mouse embryonic fibroblasts (MEFs). These mutations accumulated in senescent MEFs accompanied with endogenous ADAR1 expression, and the frequency in senescent Bcl6-deficient MEFs was higher than senescent wild-type MEFs. Thus, Bcl6 protects senescent cells from accumulation of adenosine-targeted DNA mutations induced by ADAR1.

SUBMITTER: Tsuruoka N

PROVIDER: S-EPMC3543032 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells.

Tsuruoka Nobuhide N Arima Masafumi M Yoshida Nobuya N Okada Seiji S Sakamoto Akemi A Hatano Masahiko M Satake Hisae H Arguni Eggi E Wang Ji-Yang JY Yang Jing-Hua JH Nishikura Kazuko K Sekiya Souei S Shozu Makio M Tokuhisa Takeshi T

The Journal of biological chemistry 20121203 2

Somatic mutations accumulate in senescent cells. Bcl6, which functions as a transcriptional repressor, has been identified as a potent inhibitor of cell senescence, but a role of Bcl6 in the accumulation of somatic mutations has remained unclear. Ig class-switch recombination simultaneously induces somatic mutations in an IgM class-switch (Ig-Sμ) region of IgG B cells. Surprisingly, mutations were detected in the Ig-Sμ region of Bcl6-deficient IgM B cells without class-switch recombination, and ...[more]

PMID: 23209284

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Dataset Information

ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells.

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ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells.

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