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

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.

Research highlights
► We show significant differences in the levels of expression of Mre11-Rad50-Nbs1 (MRN) complex subunits among various cancer cells and somatic cells.
► We show siRNA-mediated depletion of any of the subunits of MRN complex results in complete ablation of other subunits of the complex.
► We show an inverse correlation between the expression of Mre11–Rad50–Nbs1 subunits and telomerase activity in cells treated with anti-cancer drug, etoposide.
► These studies raise the exciting possibility of developing anticancer drugs targeting MRN complex subunits to sensitize cancer cells to radio- and/or chemotherapy.