title: Anti-apoptotic protein BCL2 down-regulates DNA end joining in cancer cells.
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.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Tadi Satish
authors.initials: TS
authors.lastname: Kumar
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Kari
authors.forename: Bibha
authors.initials: B
authors.lastname: Choudhary
authors.forename: Mridula
authors.initials: M
authors.lastname: Nambiar
authors.forename: T S
authors.initials: TS
authors.lastname: Akila
authors.forename: Sathees C
authors.initials: SC
authors.lastname: Raghavan
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D015536:Down-Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2