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Dantzer, F. et al.

Dantzer, Mark, Quenet, Scherthan, Huber, Liebe, Monaco, Chicheportiche, Sassone-Corsi, de Murcia, M??nissier-de Murcia,

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

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.[1]

References

Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis. Dantzer, F., Mark, M., Quenet, D., Scherthan, H., Huber, A., Liebe, B., Monaco, L., Chicheportiche, A., Sassone-Corsi, P., de Murcia, G., M??nissier-de Murcia, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]

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