Meiotic Cohesin SMC1 beta Provides Prophase I Centromeric Cohesion and Is Required for Multiple Synapsis-Associated Functions

作者：Biswas Uddipta; Wetzker Cornelia; Lange Julian; Christodoulou Eleni G; Seifert Michael; Beyer Andreas; Jes**erger Rolf^*

来源：PLoS Genetics, 2013, 9(12): e1003985.

DOI：10.1371/journal.pgen.1003985

Cohesin subunit SMC1 beta is specific and essential for meiosis. Previous studies showed functions of SMC1 beta in determining the axis-loop structure of synaptonemal complexes (SCs), in providing sister chromatid cohesion (SCC) in metaphase I and thereafter, in protecting telomere structure, and in synapsis. However, several central questions remained unanswered and concern roles of SMC1 beta in SCC and synapsis and processes related to these two processes. Here we show that SMC1 beta substantially supports prophase I SCC at centromeres but not along chromosome arms. Arm cohesion and some of centromeric cohesion in prophase I are provided by non-phosphorylated SMC1 alpha. Besides supporting synapsis of autosomes, SMC1 beta is also required for synapsis and silencing of sex chromosomes. In absence of SMC1 beta, the silencing factor gamma H2AX remains associated with asynapsed autosomes and fails to localize to sex chromosomes. Microarray expression studies revealed up-regulated sex chromosome genes and many down-regulated autosomal genes. SMC1 beta is further required for non-homologous chromosome associations observed in absence of SPO11 and thus of programmed double-strand breaks. These breaks are properly generated in SMC1 beta(-/-) spermatocytes, but their repair is delayed on asynapsed chromosomes. SMC1 alpha alone cannot support non-homologous associations. Together with previous knowledge, three main functions of SMC1 beta have emerged, which have multiple consequences for spermatocyte biology: generation of the loop-axis architecture of SCs, homologous and non-homologous synapsis, and SCC starting in early prophase I.

• 出版日期2013-12