Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2006

Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis.

Abstract

Besides the established central role of poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 in the maintenance of genomic integrity, accumulating evidence indicates that poly(ADP-ribosyl)ation may modulate epigenetic modifications under physiological conditions. Here, we provide in vivo evidence for the pleiotropic involvement of Parp-2 in both meiotic and postmeiotic processes. We show that Parp-2-deficient mice exhibit severely impaired spermatogenesis, with a defect in prophase of meiosis I characterized by massive apoptosis at pachytene and metaphase I stages. Although Parp-2(-/-) spermatocytes exhibit normal telomere dynamics and normal chromosome synapsis, they display defective meiotic sex chromosome inactivation associated with derailed regulation of histone acetylation and methylation and up-regulated X- and Y-linked gene expression. Furthermore, a drastically reduced number of crossover-associated Mlh1 foci are associated with chromosome missegregation at metaphase I. Moreover, Parp-2(-/-) spermatids are severely compromised in differentiation and exhibit a marked delay in nuclear elongation. Altogether, our findings indicate that, in addition to its well known role in DNA repair, Parp-2 exerts essential functions during meiosis I and haploid gamete differentiation.

Dates and versions

hal-00179859 , version 1 (16-10-2007)

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Françoise Dantzer, Manuel Mark, Delphine Quenet, Harry Scherthan, Aline Huber, et al.. Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis.. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103 (40), pp.14854-9. ⟨10.1073/pnas.0604252103⟩. ⟨hal-00179859⟩
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