Riedel Christian G, Katis Vittorio L, Katou Yuki, Mori Saori, Itoh Takehiko, Helmhart Wolfgang, Gálová Marta, Petronczki Mark, Gregan Juraj, Cetin Bulent, Mudrak Ingrid, Ogris Egon, Mechtler Karl, Pelletier Laurence, Buchholz Frank, Shirahige Katsuhiko, Nasmyth Kim
Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Nature. 2006 May 4;441(7089):53-61. doi: 10.1038/nature04664. Epub 2006 Mar 15.
Segregation of homologous maternal and paternal centromeres to opposite poles during meiosis I depends on post-replicative crossing over between homologous non-sister chromatids, which creates chiasmata and therefore bivalent chromosomes. Destruction of sister chromatid cohesion along chromosome arms due to proteolytic cleavage of cohesin's Rec8 subunit by separase resolves chiasmata and thereby triggers the first meiotic division. This produces univalent chromosomes, the chromatids of which are held together by centromeric cohesin that has been protected from separase by shugoshin (Sgo1/MEI-S332) proteins. Here we show in both fission and budding yeast that Sgo1 recruits to centromeres a specific form of protein phosphatase 2A (PP2A). Its inactivation causes loss of centromeric cohesin at anaphase I and random segregation of sister centromeres at the second meiotic division. Artificial recruitment of PP2A to chromosome arms prevents Rec8 phosphorylation and hinders resolution of chiasmata. Our data are consistent with the notion that efficient cleavage of Rec8 requires phosphorylation of cohesin and that this is blocked by PP2A at meiosis I centromeres.
在减数分裂I期间，同源的母本和父本着丝粒向相反两极的分离依赖于同源非姐妹染色单体之间复制后的交叉互换，这会形成交叉点，进而形成二价染色体。由于分离酶对黏连蛋白的Rec8亚基进行蛋白水解切割，导致沿染色体臂的姐妹染色单体黏连被破坏，从而解开交叉点，进而触发第一次减数分裂。这产生单价染色体，其染色单体通过着丝粒黏连蛋白结合在一起，而该黏连蛋白受到守护蛋白（Sgo1/MEI-S332）的保护而免受分离酶的作用。我们在裂殖酵母和芽殖酵母中均表明，Sgo1将一种特定形式的蛋白磷酸酶2A（PP2A）招募到着丝粒。其失活会导致减数分裂后期I着丝粒黏连蛋白的丢失以及减数分裂第二次分裂时姐妹着丝粒的随机分离。将PP2A人工招募到染色体臂会阻止Rec8磷酸化，并阻碍交叉点的解开。我们的数据与以下观点一致，即Rec8的有效切割需要黏连蛋白的磷酸化，而这在减数分裂I着丝粒处被PP2A阻断。
