Anti-apoptotic Protein BCL2 Down-regulates DNA End Joining in Cancer Cells

Kumar, Tadi Satish and Kari, Vijayalakshmi and Choudhary, Bibha and Nambiar, Mridula and Akila, TS and Raghavan, Sathees C (2010) Anti-apoptotic Protein BCL2 Down-regulates DNA End Joining in Cancer Cells. In: Journal of Biological Chemistry, 285 (42). pp. 32657-32670.

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Abstract

Cancer cells are often associated with secondary chromosomal rearrangements, such as deletions, inversions, and translocations, which could be the consequence of unrepaired/misrepaired DNA double strand breaks (DSBs). Nonhomologous DNA end joining is one of the most common pathways to repair DSBs in higher eukaryotes. By using oligomeric DNA substrates mimicking various endogenous DSBs in a cell-free system, we studied end joining (EJ) in different cancer cell lines. We found that the efficiency of EJ varies among cancer cells; however, there was no remarkable difference in the mechanism and expression of EJ proteins. Interestingly, cancer cells with lower levels of EJ possessed elevated expression of BCL2 and vice versa. Removal of BCL2 by immunoprecipitation or protein fractionation led to elevated EJ. More importantly, we show that overexpression of BCL2 or the addition of purified BCL2 led to the down-regulation of EJ. Further, we found that BCL2 interacts with KU proteins both in vitro and in vivo. Hence, our 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.

Item Type:	Journal Article
Publication:	Journal of Biological Chemistry
Publisher:	The American Society for Biochemistry and Molecular Biology
Additional Information:	Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	26 Oct 2010 08:43
Last Modified:	26 Oct 2010 08:43
URI:	http://eprints.iisc.ac.in/id/eprint/33421

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