Rad51 and DNA-PKcs are involved in the generation of specific telomere aberrations induced by the quadruplex ligand 360A that impair mitotic cell progression and lead to cell death

• DOI: 10.1007/s00018-011-0767-6
• Publication Date: 2011-07-19T07:53:20Z
• Authors: Laurent R. Gauthier; Christine Granotier; Françoise Hoffschir; Olivier Etienne; Ali Ayouaz; Chantal Desmaze; Patrick Mailliet; Denis S. Biard; François D. Boussin
• Keywords: Telomere-binding protein; RAD52

Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways. Replication is a critical period for because of the requirement reconstitution functional telomere conformations, process that involves proteins. Using knockdown DNA-PKcs Rad51 expression in three different cell lines, we demonstrate respective involvement NHEJ HR formation aberrations induced by G-quadruplex ligand 360A during or after replication. contributed to specific chromatid-type (telomere losses doublets) affecting lagging strand telomeres, whereas DNA-PKcs-dependent was responsible sister fusions as direct consequence and/or stabilization on parental G strands. activation at altered mitotic progression treated cells. In particular, NHEJ-mediated were associated with metaphase-anaphase transition anaphase bridges resulted death mitosis early G1. Collectively, these data elucidate molecular cellular mechanisms triggered targeting 360A, leading cancer death.