Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity |
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Authors: | Youn Cha-Kyung Cho Hyun-Ju Kim Soo-Hyun Kim Hong-Beum Kim Mi-Hwa Chang In-Youb Lee Jung-Sup Chung Myung-Hee Hahm Kyung-Soo You Ho Jin |
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Affiliation: | Department of Pharmacology, School of medicine, Chosun University, 375 Seusuk-dong, Gwangju 501-759, South Korea. |
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Abstract: | Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches. The pathway linking Bcl-2 expression to the suppression of mismatch repair (MMR) activity involves the hypophosphorylation of pRb, and then the enhancement of the E2F-pRb complex. This is followed by a decrease in hMSH2 expression. MMR has a key role in protection against deleterious mutation accumulation and in maintaining genomic stability. Therefore, the decreased MMR activity by Bcl-2 may be an underlying mechanism for Bcl-2-promoted oncogenesis. |
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