Differential regulation of MRN (Mre11-Rad50-Nbs1) complex subunits and telomerase activity in cancer cells

Kavitha, CV and Choudhary, Bibha and Raghavan, Sathees C and Muniyappa, K (2010) Differential regulation of MRN (Mre11-Rad50-Nbs1) complex subunits and telomerase activity in cancer cells. In: Biochemical and Biophysical Research Communications, 399 (4). pp. 575-580.

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Abstract

Several lines of evidence suggest that cancer progression is associated with up-regulation or reactivation of telomerase and the underlying mechanism remains an active area of research. The heterotrimeric MRN complex, consisting of Mre11, Rad50 and Nbs1, which is required for the repair of double-strand breaks, plays a key role in telomere length maintenance. In this study, we show significant differences in the levels of expression of MRN complex subunits among various cancer cells and somatic cells. Notably, siRNA-mediated depletion of any of the subunits of MRN complex led to complete ablation of other subunits of the complex. Treatment of leukemia and prostate cancer cells with etoposide lead to increased expression of MRN complex subunits, with concomitant decrease in the levels of telomerase activity, compared to breast cancer cells. These studies raise the possibility of developing anti-cancer drugs targeting MRN complex subunits to sensitize a subset of cancer cells to radio- and/or chemotherapy. (C) 2010 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Publication:	Biochemical and Biophysical Research Communications
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Keywords:	Cancer; MRN complex;Etoposide;TRAP assay;Telomerase.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	11 Oct 2010 05:55
Last Modified:	11 Oct 2010 05:55
URI:	http://eprints.iisc.ac.in/id/eprint/33151

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