title: 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.
authors.affiliation: Intégrité du Génome, Unité Mixte de Recherche 7175, Ecole Supérieure de Biotechnologie de Strasbourg, F-67412 Illkirch, France. f.dantzer@esbs.u-strasbg.fr
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantzer
authors.forename: Manuel
authors.initials: M
authors.lastname: Mark
authors.forename: Delphine
authors.initials: D
authors.lastname: Quenet
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
authors.forename: Aline
authors.initials: A
authors.lastname: Huber
authors.forename: Bodo
authors.initials: B
authors.lastname: Liebe
authors.forename: Lucia
authors.initials: L
authors.lastname: Monaco
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chicheportiche
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
authors.forename: Gilbert
authors.initials: G
authors.lastname: de Murcia
authors.forename: Josiane
authors.initials: J
authors.lastname: Ménissier-de Murcia
mesh_terms: D000818:Animals; D017209:Apoptosis; D020090:Chromosome Segregation / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics; D007248:Infertility, Male; D008297:Male; D008540:Meiosis / Q000502:physiology*; D008677:Metaphase / Q000502:physiology; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000378:metabolism*; D012730:Sex Chromosomes / Q000235:genetics; D013090:Spermatocytes / Q000166:cytology; D013091:Spermatogenesis / Q000502:physiology*; D016615:Telomere / Q000378:metabolism; D013737:Testis / Q000166:cytology
chemical_list: D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse