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

@article{Youn2005Bcl2ES,
  title={Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity},
  author={Cha Kyung Youn and Hyun-Ju Cho and Soo-Hyun Kim and Hong-Beum Kim and Mi-hwa Kim and In Youb Chang and Jung-Sup Lee and Myung Hee Chung and Kyung-soo Hahm and Ho Jin You},
  journal={Nature Cell Biology},
  year={2005},
  volume={7},
  pages={137-147}
}
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… 
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74 Citations

Bcl2 Suppresses DNA Repair by Enhancing c-Myc Transcriptional Activity*
TLDR
Bcl2, in addition to its survival function, may also suppress DNA repair in a novel mechanism involving c-Myc and APE1, which may lead to an accumulation of DNA damage in living cells, genetic instability, and tumorigenesis.
Bcl2 negatively regulates DNA double-strand-break repair through a nonhomologous end-joining pathway.
Bcl2 Inhibits Abasic Site Repair by Down-regulating APE1 Endonuclease Activity*
TLDR
Bcl2 inhibition of AP site repair may occur in a novel mechanism by down-regulating APE1 endonuclease activity, which may promote genetic instability and tumorigenesis.
Bcl-2 inhibits nuclear homologous recombination by localizing BRCA1 to the endomembranes.
TLDR
The results reveal a new mode of BRCA1 regulation and for HR in the maintenance of genome stability and support an apoptosis-stimulatory role for the cytosolic form of BrcA1, suggesting a new tumor suppressor function of B RCA1.
Anti-apoptotic Protein BCL2 Down-regulates DNA End Joining in Cancer Cells*
TLDR
The results suggest that EJ in cancer cells could be negatively regulated by the anti-apoptotic protein, BCL2, and this may contribute toward increased chromosomal abnormalities in cancer.
The secret life of Bcl-2: apoptosis-independent inhibition of DNA repair by Bcl-2 family members.
Identification of an ataxia telangiectasia-mutated protein mediated surveillance system to regulate Bcl-2 overexpression
TLDR
Evidence is provided suggesting that activation of ATM suppresses Bcl-2-induced tumorigenesis, and that attenuation of ATM function may be an important event in breast cancer progression, as well as indicating an ATM-mediated surveillance system for regulating B cl-2 overexpression.
A mismatched role for Bcl-2
TLDR
This study has shown that by retaining E2F-1 in a transcriptionally inactive state, through the induction of hypophosphorylated retinoblastoma protein, Bcl-2 hinders the expression of a key component of mismatch repair, MSH2.
Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous recombination, independently of apoptosis regulation
TLDR
It is shown that the induction of both recombinant cells and recombinant colonies was impaired when expressing Bcl-2 family members, in hamster as well as in human cells, revealing a mechanism of HR downregulation by potentially proapoptotic proteins, distinct from and parallel to degradation of recombination proteins.
Senescence-Dependent MutSα Dysfunction Attenuates Mismatch Repair
TLDR
Results indicate that the suppression of E2F1 transcriptional activity in senescence cells lead to stable repression of MSH2, followed by a induction of MutSα dysfunction, which results in a reduced cellular MMR capacity in senescent cells.
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