The involvement of the Mre11/Rad50/Nbs1 complex in the generation of G-overhangs at human telomeres

A central function of telomeres is to prevent chromosome ends from being recognized as DNA double-strand breaks (DSBs). Several proteins involved in processing DSBs associate with telomeres, but the roles of these factors at telomeres are largely unknown. To investigate whether the Mre11/Rad50/Nbs1 (MRN) complex is involved in the generation of proper 3' G-overhangs at human telomere ends, we used RNA interference to decrease expression of MRN and analysed their effects. Reduction of MRN resulted in a transient shortening of G- overhang length in telomerase- positive cells. The terminal nucleotides of both C- and G- rich strands remain unaltered in Mre11- diminished cells, indicating that MRN is not responsible for specifying the final end- processing event. The reduction in overhang length was not seen in telomerase- negative cells, but was observed after the expression of exogenous telomerase, which suggested that the MRN complex might be involved in the recruitment or action of telomerase.