title: X-ray induced DNA damage and repair in germ cells of PARP1(-/-) male mice.
abstract: Poly(ADP-ribose)polymerase-1 (PARP1) is a nuclear protein implicated in DNA repair, recombination, replication, and chromatin remodeling. The aim of this study was to evaluate possible differences between PARP1(-/-) and wild-type mice regarding induction and repair of DNA lesions in irradiated male germ cells. Comet assay was applied to detect DNA damage in testicular cells immediately, and two hours after 4 Gy X-ray irradiation. A similar level of spontaneous and radiation-induced DNA damage was observed in PARP1(-/-) and wild-type mice. Conversely, two hours after irradiation, a significant level of residual damage was observed in PARP1(-/-) cells only. This finding was particularly evident in round spermatids. To evaluate if PARP1 had also a role in the dynamics of H2AX phosphorylation in round spermatids, in which γ-H2AX foci had been shown to persist after completion of DNA repair, we carried out a parallel analysis of γ-H2AX foci at 0.5, 2, and 48 h after irradiation in wild-type and PARP1(-/-) mice. No evidence was obtained of an effect of PARP1 depletion on H2AX phosphorylation induction and removal. Our results suggest that, in round spermatids, under the tested experimental conditions, PARP1 has a role in radiation-induced DNA damage repair rather than in long-term chromatin modifications signaled by phosphorylated H2AX.
authors.affiliation: Unit of Radiation Biology and Human Health, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, CR Casaccia, Via Anguillarese 301, Roma 00123, Italy. paola.villani@enea.it
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fresegna
authors.forename: Roberto
authors.initials: R
authors.lastname: Ranaldi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Eleuteri
authors.forename: Lorena
authors.initials: L
authors.lastname: Paris
authors.forename: Francesca
authors.initials: F
authors.lastname: Pacchierotti
authors.forename: Eugenia
authors.initials: E
authors.lastname: Cordelli
mesh_terms: D000818:Animals; D020552:Comet Assay; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects*; D005434:Flow Cytometry; D005854:Germ Cells / Q000378:metabolism* / Q000528:radiation effects*; D006657:Histones; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D006657:Histones; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases