Katis Vittorio L, Galova Marta, Rabitsch Kirsten P, Gregan Juraj, Nasmyth Kim
Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria.
Curr Biol. 2004 Apr 6;14(7):560-72. doi: 10.1016/j.cub.2004.03.001.
The halving of chromosome number that occurs during meiosis depends on three factors. First, homologs must pair and recombine. Second, sister centromeres must attach to microtubules that emanate from the same spindle pole, which ensures that homologous maternal and paternal pairs can be pulled in opposite directions (called homolog biorientation). Third, cohesion between sister centromeres must persist after the first meiotic division to enable their biorientation at the second.
A screen performed in fission yeast to identify meiotic chromosome missegregation mutants has identified a conserved protein called Sgo1 that is required to maintain sister chromatid cohesion after the first meiotic division. We describe here an orthologous protein in the budding yeast S. cerevisiae (Sc), which has not only meiotic but also mitotic chromosome segregation functions. Deletion of Sc SGO1 not only causes frequent homolog nondisjunction at meiosis I but also random segregation of sister centromeres at meiosis II. Meiotic cohesion fails to persist at centromeres after the first meiotic division, and sister centromeres frequently separate precociously. Sgo1 is a kinetochore-associated protein whose abundance declines at anaphase I but, nevertheless, persists on chromatin until anaphase II.
The finding that Sgo1 is localized to the centromere at the time of the first division suggests that it may play a direct role in preventing the removal of centromeric cohesin. The similarity in sequence composition, chromosomal location, and mutant phenotypes of sgo1 mutants in two distant yeasts with that of MEI-S332 in Drosophila suggests that these proteins define an orthologous family conserved in most eukaryotic lineages.
减数分裂过程中染色体数目减半取决于三个因素。首先,同源染色体必须配对并重组。其次,姐妹染色单体的着丝粒必须附着于来自同一纺锤体极的微管上,这确保了同源的母本和父本染色体对能够被拉向相反方向(称为同源染色体双定向)。第三,姐妹染色单体着丝粒之间的黏连在第一次减数分裂后必须持续存在,以使它们在第二次减数分裂时能够双定向。
在裂殖酵母中进行的一项筛选减数分裂染色体错分离突变体的实验,鉴定出一种名为Sgo1的保守蛋白,它是第一次减数分裂后维持姐妹染色单体黏连所必需的。我们在此描述了芽殖酵母酿酒酵母(Sc)中的一种直系同源蛋白,它不仅具有减数分裂染色体分离功能,还具有有丝分裂染色体分离功能。缺失Sc SGO1不仅会导致减数分裂I期同源染色体频繁不分离,还会导致减数分裂II期姐妹染色单体着丝粒随机分离。减数分裂黏连在第一次减数分裂后无法在着丝粒处持续存在,姐妹染色单体着丝粒经常过早分离。Sgo1是一种与动粒相关的蛋白,其丰度在后期I时下降,但仍会在染色质上持续存在直到后期II。
Sgo1在第一次分裂时定位于着丝粒这一发现表明,它可能在防止着丝粒黏连蛋白被去除方面发挥直接作用。两种远缘酵母中sgo1突变体在序列组成、染色体定位和突变体表型上与果蝇中的MEI-S332相似,这表明这些蛋白定义了一个在大多数真核生物谱系中保守的直系同源家族。