Different DNA-PKcs functions in the repair of radiation-induced and spontaneous DSBs within interstitial telomeric sequences |
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Authors: | Déborah Revaud Luis M Martins François D Boussin Laure Sabatier Chantal Desmaze |
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Institution: | 1.Laboratoire de Radiopathologie,Institut de Radiobiologie Cellulaire et Moléculaire CEA-DSV, INSERM UMR 967, Université Paris VII UMR 967, Université Paris XI UMR 967,Fontenay-aux-Roses,France;2.CEA-DSV/iRCM/Laboratoire de Radiobiologie et d’Oncologie,Fontenay-aux-Roses,France;3.CEA-DSV/iRCM,Fontenay-aux-Roses,France |
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Abstract: | Interstitial telomeric sequences (ITSs) in hamster cells are hot spots for spontaneous and induced chromosome aberrations
(CAs). Most data on ITS instability to date have been obtained in DNA repair-proficient cells. The classical non-homologous
end joining repair pathway (C-NHEJ), which is the principal double strand break (DSB) repair mechanism in mammalian cells,
is thought to restore the morphologically correct chromosome structure. The production of CAs thus involves DNA-PKcs-independent
repair pathways. In our current study, we investigated the participation of DNA-PKcs from the C-NHEJ pathway in the repair
of spontaneous or radiation-induced DSBs in ITSs using wild-type and DNA-PKcs mutant Chinese hamster ovary cells. Our data
demonstrate that DNA-PKcs stabilizes spontaneous DSBs within ITSs from the chromosome 9 long arm, leading to the formation
of terminal deletions. In addition, we show that DNA-PKcs-dependent C-NHEJ is employed following radiation-induced DSBs in
other ITSs and restores morphologically correct chromosomes, whereas DNA-PKcs independent mechanisms co-exist in DNA-PKcs
proficient cells leading to an excess of CAs within ITSs. |
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