| First Author | Tsuruoka N | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 2 | Pages | 826-36 |
| PubMed ID | 23209284 | Mgi Jnum | J:193867 |
| Mgi Id | MGI:5469797 | Doi | 10.1074/jbc.M112.365718 |
| Citation | Tsuruoka N, et al. (2013) ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells. J Biol Chem 288(2):826-36 |
| abstractText | 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-Smu) region of IgG B cells. Surprisingly, mutations were detected in the Ig-Smu 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. |
