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

被引:98
作者
Dantzer, Francoise [1 ]
Mark, Manuel
Quenet, Delphine
Scherthan, Harry
Huber, Aline
Liebe, Bodo
Monaco, Lucia
Chicheportiche, Alexandra
Sassone-Corsi, Paolo
de Murcia, Gilbert
Menissier-de Murcia, Josiane
机构
[1] Ecole Super Biotechnol Strasbourg, Unite Mixte Rech 7175, F-67412 Illkirch Graffenstaden, France
[2] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France
[3] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[4] Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France
[5] INSERM, U566, F-92265 Fontenay Aux Roses, France
关键词
SEX-CHROMOSOME INACTIVATION; MICE LACKING; DNA-REPAIR; MALE-STERILITY; CROSSING-OVER; CHROMATIN; SPERMATOCYTES; PARP; H2AX; TRANSITION;
D O I
10.1073/pnas.0604252103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Parp2(-/-) 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 1. 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.
引用
收藏
页码:14854 / 14859
页数:6
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