BRCA1-mediated chromatin silencing is limited to oocytes with a small number of asynapsed chromosomes
BRCA1-mediated chromatin silencing is limited to oocytes with a small number of asynapsed chromosomes
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DOI：
10.1242/jcs.049353
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发表时间：
2009-07-15
影响因子：
4
通讯作者：
Hoog, Christer
中科院分区：
文献类型：
--
作者：
Kouznetsova, Anna;Wang, Hong;Hoog, Christer
在雄性减数分裂期间性染色体的转录沉默被认为是在雄性和雌性生殖细胞中都活跃的一般机制的表现，称为未突触染色质的减数分裂沉默（MSUC）。MSUC是由肿瘤抑制蛋白BRCA 1募集到未突触染色体的轴上而启动的。我们现在表明，Sycp3，染色体轴的结构组成部分，是本地化的BRCA1到未突触粗线期染色体所需的。重要的是，我们发现携带过量的两到三对不联会同源染色体的卵母细胞不能招募足够的BRCA1到不联会轴来激活MSUC。此外，MSUC功能的丧失只能短暂地挽救卵母细胞在出生后早期发育过程中的消除。BRCA1依赖性突触监视系统不能对更高程度的不联会做出反应，并且不能去除异常卵母细胞，这一事实表明，MSUC作为雌性生殖细胞的质量控制机制的输入有限。
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.