Rabitsch Kirsten P, Gregan Juraj, Schleiffer Alex, Javerzat Jean-Paul, Eisenhaber Frank, Nasmyth Kim
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Curr Biol. 2004 Feb 17;14(4):287-301. doi: 10.1016/j.cub.2004.01.051.
Meiosis produces haploid gametes from diploid progenitor cells. This reduction is achieved by two successive nuclear divisions after one round of DNA replication. Correct chromosome segregation during the first division depends on sister kinetochores being oriented toward the same spindle pole while homologous kinetochores must face opposite poles. Segregation during the second division depends on retention of sister chromatid cohesion between centromeres until the onset of anaphase II, which in Drosophila melanogaster depends on a protein called Mei-S332 that binds to centromeres.
We report the identification of two homologs of Mei-S332 in fission yeast using a knockout screen. Together with their fly ortholog they define a protein family conserved from fungi to mammals. The two identified genes, sgo1 and sgo2, are required for retention of sister centromere cohesion between meiotic divisions and kinetochore orientation during meiosis I, respectively. The amount of meiotic cohesin's Rec8 subunit retained at centromeres after meiosis I is reduced in Deltasgo1, but not in Deltasgo2, cells, and Sgo1 appears to regulate cleavage of Rec8 by separase. Both Sgo1 and Sgo2 proteins localize to centromere regions. The abundance of Sgo1 protein normally declines after the first meiotic division, but extending its expression by altering its 3'UTR sequences does not greatly affect meiosis II. Its mere presence within the cell might therefore be insufficient to protect centromeric cohesion.
A conserved protein family based on Mei-S332 has been identified. The two fission yeast homologs are implicated in meiosis I kinetochore orientation and retention of centromeric sister chromatid cohesion until meiosis II.
减数分裂从二倍体祖细胞产生单倍体配子。这种染色体数目减半是通过一轮DNA复制后的两次连续核分裂实现的。第一次分裂过程中正确的染色体分离取决于姐妹动粒朝向同一纺锤极,而同源动粒必须朝向相反的极。第二次分裂过程中的分离取决于着丝粒之间的姐妹染色单体黏连保留到后期II开始,在黑腹果蝇中这依赖于一种名为Mei-S332的蛋白质与着丝粒结合。
我们通过基因敲除筛选在裂殖酵母中鉴定出了Mei-S332的两个同源物。它们与果蝇中的直系同源物共同定义了一个从真菌到哺乳动物都保守的蛋白质家族。所鉴定的两个基因,sgo1和sgo2,分别是减数分裂各次分裂间姐妹着丝粒黏连的保留以及减数分裂I期间动粒定向所必需的。在Δsgo1细胞中,减数分裂I后保留在着丝粒处的减数分裂黏连蛋白Rec8亚基的量减少,但在Δsgo2细胞中没有减少,并且Sgo1似乎调节分离酶对Rec8的切割。Sgo1和Sgo2蛋白都定位于着丝粒区域。通常减数分裂第一次分裂后Sgo1蛋白的丰度会下降,但通过改变其3'UTR序列延长其表达对减数分裂II没有太大影响。因此,它仅仅存在于细胞内可能不足以保护着丝粒黏连。
已鉴定出一个基于Mei-S332的保守蛋白质家族。裂殖酵母中的两个同源物与减数分裂I动粒定向以及着丝粒姐妹染色单体黏连保留到减数分裂II有关。