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Abstract

The present study aimed at determining the effect of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta (pol�²��208-304) specific for ovarian cancer. Pol�²��208-304 has deletion of exons 11-13 which lies in catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT assay, colony forming assay and apoptosis. Pol�²��208-304 cells exhibit greater sensitivity to alkylating agent and less sensitivity towards H2O2 and UV when compared with HeLa cells alone. It has also been shown that cell death in Pol�²��208-304 transfected HeLa cells is mediated by the caspase-9 cascade. The exon-11 have nucleotidyl selection activity, exon-12 and 13 have dNTPs selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. Missing of this part may adversely affect catalytic activity of DNA polymerase beta hence this variant may act as a dominant negative mutant. This would represent a clinical significance if translated into clinical setting because resistance to radiation or chemo during the relapse of the disease could be potentially overcome by this approach.

Biography

Kalyani Khanra has completed her PhD from Vidyasagar University. She is a Postdoctoral Fellow in a UGC-DAE sponsored project performing research at Department of Biotechnology, Panskura Banamali College. She has published 18 research papers in international journals and published two book chapters. She is also Co-applicant of two national patents.

Email: kkhanra@rediffmail.com