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Nat Cell Biol. 2005 Feb;7(2):137-47. Epub 2004 Dec 26.

Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity.

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1
Department of Pharmacology, School of medicine, Chosun University, 375 Seusuk-dong, Gwangju 501-759, South Korea.

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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PMID:
15619620
DOI:
10.1038/ncb1215
[Indexed for MEDLINE]

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