Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis.
Proc Natl Acad Sci U S A
; 103(40): 14854-9, 2006 Oct 03.
Article
en En
| MEDLINE
| ID: mdl-17001008
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Espermatogénesis
/
Poli(ADP-Ribosa) Polimerasas
/
Meiosis
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia