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.
Dantzer
Françoise
F
Intégrité du Génome, Unité Mixte de Recherche 7175, Ecole Supérieure de Biotechnologie de Strasbourg, F-67412 Illkirch, France. f.dantzer@esbs.u-strasbg.fr
Mark
Manuel
M
Quenet
Delphine
D
Scherthan
Harry
H
Huber
Aline
A
Liebe
Bodo
B
Monaco
Lucia
L
Chicheportiche
Alexandra
A
Sassone-Corsi
Paolo
P
de Murcia
Gilbert
G
Ménissier-de Murcia
Josiane
J
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
D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse