BRCA1-mediated chromatin silencing is limited to oocytes with a small number of asynapsed chromosomes

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Anna Kouznetsova - , Karolinska Institutet (Autor:in)
  • Hong Wang - , Karolinska Institutet (Autor:in)
  • Marina Bellani - , National Institutes of Health (NIH) (Autor:in)
  • R Daniel Camerini-Otero - , National Institutes of Health (NIH) (Autor:in)
  • Rolf Jessberger - , Institut für Physiologische Chemie (Autor:in)
  • Christer Höög - , Karolinska Institutet (Autor:in)

Abstract

Transcriptional silencing of the sex chromosomes during male meiosis is regarded as a manifestation of a general mechanism active in both male and female germ cells, called meiotic silencing of unsynapsed chromatin (MSUC). MSUC is initiated by the recruitment of the tumor suppressor protein BRCA1 to the axes of unsynapsed chromosomes. We now show that Sycp3, a structural component of the chromosome axis, is required for localization of BRCA1 to unsynapsed pachytene chromosomes. Importantly, we find that oocytes carrying an excess of two to three pairs of asynapsed homologous chromosomes fail to recruit enough BRCA1 to the asynapsed axes to activate MSUC. Furthermore, loss of MSUC function only transiently rescues oocytes from elimination during early postnatal development. The fact that the BRCA1-dependent synapsis surveillance system cannot respond to higher degrees of asynapsis and is dispensable for removal of aberrant oocytes argues that MSUC has a limited input as a quality control mechanism in female germ cells.

Details

OriginalspracheEnglisch
Seiten (von - bis)2446-2452
Seitenumfang7
FachzeitschriftJournal of Cell Science
Jahrgang122
AusgabenummerPt 14
PublikationsstatusVeröffentlicht - 15 Juli 2009
Peer-Review-StatusJa

Externe IDs

Scopus 69649091568
PubMed 19531582

Schlagworte

Schlagwörter

  • Animals, Ataxia Telangiectasia Mutated Proteins, BRCA1 Protein/metabolism, Cell Cycle Proteins/genetics, Cell Survival, Chromatin/metabolism, DNA-Binding Proteins, Female, Gene Silencing, Histones/metabolism, Male, Meiosis/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins/genetics, Oocytes/metabolism, Pachytene Stage/genetics, Phosphorylation, Protein Serine-Threonine Kinases/metabolism, Sex Chromosomes, Transcription, Genetic