X-ray induced DNA damage and repair in germ cells of PARP1-/- male mice

Paola Villani, Anna Maria Fresegna, Roberto Ranaldi, Patrizia Eleuteri, Lorena Paris, Francesca Pacchierotti, Eugenia Cordelli

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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. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
Original languageEnglish
Pages (from-to)18078 - 18092
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume14
Issue number9
DOIs
Publication statusPublished - 2013
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry

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