BRCA1-mediated chromatin silencing is limited to oocytes with a small number of asynapsed chromosomes.
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.
Kouznetsova
Anna
A
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, Stockholm, S-171 77, Sweden.
Wang
Hong
H
Bellani
Marina
M
Camerini-Otero
R Daniel
RD
Jessberger
Rolf
R
Höög
Christer
C
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D049471:Pachytene Stage / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012730:Sex Chromosomes; D014158:Transcription, Genetic
D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; C438001:Smc1l2 protein, mouse; C489754:Sycp1 protein, mouse; C490062:Sycp3 protein, mouse; C576597:ATR protein, human; C475961:gamma-H2AX protein, mouse