title: Different DNA-PKcs functions in the repair of radiation-induced and spontaneous DSBs within interstitial telomeric sequences.
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.
authors.affiliation: Laboratoire de Radiopathologie, Institut de Radiobiologie Cellulaire et Moléculaire CEA-DSV, Université Paris VII UMR 967, Fontenay-aux-Roses, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Revaud
authors.forename: Luis M
authors.initials: LM
authors.lastname: Martins
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Laure
authors.initials: L
authors.lastname: Sabatier
authors.forename: Chantal
authors.initials: C
authors.lastname: Desmaze
mesh_terms: D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
chemical_list: D051747:DNA-Activated Protein Kinase