Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination.

摘要: Ku70-Ku80 heterodimers promote the non-homologous end-joining (NHEJ) of DNA breaks and, as shown here, fusion dysfunctional telomeres. Paradoxically, this heterodimer is also located at functional mammalian telomeres and interacts with components shelterin, protein complex that protects To determine whether Ku contributes to telomere protection, we analysed Ku70(-/-) mouse cells. Telomeres cells had a normal structure did not activate damage signal. However, Ku70 repressed exchanges between sister - form homologous recombination implicated in alternative lengthening (ALT) pathway. Sister occurred approximately 15% chromosome ends when telomeric TRF2 were absent. Combined deficiency another NHEJ factor, ligase IV, elicit phenotype. elevated TRF2, indicating act parallel repress recombination. We conclude are highly susceptible recombination, which can endanger cell viability if an unequal exchange generates critically shortened telomere. Therefore, Ku- TRF2-mediated repression important aspect protection.