Role of ATM in the telomere response to the G-quadruplex ligand 360A.

Gaëlle Pennarun (1) , Christine Granotier (1) , Françoise Hoffschir (1) , Eliane Mandine (2) , Denis Biard (1) , Laurent R Gauthier (1) , François D Boussin (1)

1 IRCM - Institut de Radiobiologie Cellulaire et Moléculaire
2 Aventis Pharma SA

Telomeres are known to prevent chromosome ends from being recognized as DNA double-strand breaks. Conversely, many DNA damage response proteins, including ATM, are thought to participate to telomere maintenance. However, the precise roles of ATM at telomeres remain unclear due to its multiple functions in cell checkpoints and apoptosis. To gain more insights into the role of ATM in telomere maintenance, we determined the effects of the G-quadruplex ligand 360A in various cell lines lacking functional ATM. We showed, by using Fluorescence in situ hybridization (FISH) and Chromosome Orientation-FISH using telomere PNA probes, that 360A induced specific telomere aberrations occurring during or after replication, mainly consisting in sister telomere fusions and also recombinations that involved preferentially the lagging strand telomeres. We demonstrate that ATM reduced telomere instability independently of apoptosis induction. Our results suggest thus that ATM has a direct role in preventing inappropriate DNA repair at telomeres, which could be related to its possible participation to the formation of protected structures at telomeres.

Domaines: Biochimie, Biologie Moléculaire

Gaëlle Pennarun, Christine Granotier, Françoise Hoffschir, Eliane Mandine, Denis Biard, et al.. Role of ATM in the telomere response to the G-quadruplex ligand 360A.. Nucleic Acids Research, 2008, 36 (5), pp.1741-54. ⟨10.1093/nar/gkn026⟩. ⟨cea-00268952⟩