Anti-apoptotic protein BCL2 down-regulates DNA end joining in cancer cells

Kumar, Tadi Satish ; Kari, Vijayalakshmi ; Chaudhary, Bibha ; Nambiar, Mridula ; Akila, T. S. ; Raghavan, Sathees C. (2010) Anti-apoptotic protein BCL2 down-regulates DNA end joining in cancer cells The Journal of Biological Chemistry, 285 (42). pp. 32657-32670. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/285/42/32657.abstract

Related URL: http://dx.doi.org/10.1074/jbc.M110.140350

Abstract

Cancer cells are often associated with secondary chromosomal rearrangements, such as deletions, inversions, and translocations, which could be the consequence of unrepaired/misrepaired DSBs. Nonhomologous DNA End Joining (NHEJ) is one of the major DSB repair pathways in higher organisms. By using oligomeric DNA substrates mimicking various endogenous DSBs we studied NHEJ in different cancer cell lines. We found that the efficiency of NHEJ varies among cancer cells; however, there was no remarkable difference in the mechanism and expression of NHEJ proteins. Interestingly, we found that cancer cells with lower levels of BCL2 possessed efficient End Joining (EJ) and vice versa. Removal of BCL2 by immunoprecipitation and protein fractionation using size exclusion column chromatography showed elevated levels of end joining. Most importantly, we showed that overexpression of BCL2 in vivo or the addition of purified BCL2 led to the downregulation of EJ in cancer cells. Further, we found that BCL2 interacts with KU proteins both in vitro and in vivo using immunoprecipitation and immunofluorescence, respectively. Hence, our results suggest that NHEJ in cancer cells could negatively regulated by the anti-apoptotic protein, BCL2 and this may contribute towards increased chromosomal abnormalities cancer.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
Keywords:DNA; DNA Damage; DNA Repair; Mutagenesis Mechanisms; Nucleic Acid; Nucleus; DNA Double Strand Break; Genomic Instability; Ligase IV; NHEJ
ID Code:103940
Deposited On:11 Apr 2017 16:22
Last Modified:11 Apr 2017 16:22

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