Role of ATM in the telomere response to the G-quadruplex ligand 360A.
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.
Pennarun
Gaëlle
G
CEA, DSV, iRCM, Laboratoire de Radiopathologie-IPSC, 92265 Fontenay-aux-Roses, France.
Granotier
Christine
C
Hoffschir
Françoise
F
Mandine
Eliane
E
Biard
Denis
D
Gauthier
Laurent R
LR
Boussin
François D
FD
D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D054856:G-Quadruplexes / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D015398:Signal Transduction; D012854:Sister Chromatid Exchange / Q000187:drug effects; D016615:Telomere / Q000737:chemistry* / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
C502660:2,6-N,N'-methyl-quinolinio-3-yl-pyridine dicarboxamide; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; D011725:Pyridines; D011804:Quinolines; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases