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Analysis of the regulation of meiosis-specific chromosome segregation

减数分裂特异性染色体分离的调控分析

基本信息

批准号：
14380324
负责人：
WATANABE Yoshinori
金额：
$ 9.6万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

During mitosis, sister kinetochores attach to microtubules that extend to opposite spindle poles and pull the chromatids apart at anaphase (equational segregation). A multisubunit complex called cohesin, including Rad21/Scc1, plays a crucial role in sister chromatid cohesion and equational segregation at mitosis. Meiosis I differs from mitosis in having a reductional pattern of chromosome segregation, in which sister kinetochores are attached to the same spindle. During meiosis, Rad21/Scc1 is largely replaced by its meiotic counterpart, Rec8. If Rec8 is inactivated in fission yeast, meiosis I is shifted from reductional to equational division. However, the reason rec8Δ cells undergo equational rather than random division has not been clarified. Here we have shown that the equational segregation at meiosis I depends on substitutive Rad21, which relocates to the centromeres if Rec8 is absent. Therefore, cohesin is a crucial determinant of the attachment manner of kinetoclores to the spindle microtubules at meiosis I in fission yeast. It is well known that sister chromatid cohesion must persist at centromeres throughout the first meiotic division (meiosis I) when only arm cohesion is destroyed. The factors that protect centromeric cohesion during meiosis I have remained, elusive. Here we identify Sgo1 (Shugoshin), a protector of the centromeric Rec8 cohesin in fission yeast, and a homologue in budding yeast. We also suggest that shugoshin is widely conserved among eukaryotes. Moreover, we identify Sgo2, a paralogue of shugoshin in fission yeast, which is required for faithful mitotic chromosome segregation. These findings provide insights into the evolution of meiosis and kinetocho regulation at mitosis and meiosis.

在有丝分裂期间，姐妹着丝粒附着在微管上，微管延伸到相反的纺锤体极，并在后期将染色单体拉开（等分离）。称为粘连蛋白的多亚基复合物（包括 Rad21/Scc1）在姐妹染色单体粘连和有丝分裂时的等式分离中发挥着至关重要的作用。减数分裂 I 与有丝分裂的不同之处在于，它具有染色体分离的减少模式，其中姐妹动粒附着在同一纺锤体上。在减数分裂期间，Rad21/Scc1 很大程度上被其减数分裂对应物 Rec8 取代。如果 Rec8 在裂殖酵母中失活，减数分裂 I 将从还原分裂转变为等分裂。然而，rec8Δ细胞进行等式分裂而不是随机分裂的原因尚未阐明。在这里，我们证明了减数分裂 I 时的等式分离取决于替代性 Rad21，如果 Rec8 不存在，Rad21 就会重新定位到着丝粒。因此，粘连蛋白是裂殖酵母减数分裂 I 时着丝粒与纺锤体微管附着方式的关键决定因素。众所周知，在第一次减数分裂（减数分裂 I）期间，当只有臂内聚力被破坏时，姐妹染色单体内聚力必须在着丝粒处持续存在。在减数分裂过程中保护着丝粒凝聚力的因素仍然难以捉摸。在这里，我们鉴定了 Sgo1 (Shugoshin)，它是裂殖酵母中着丝粒 Rec8 粘连蛋白的保护剂，也是芽殖酵母中的同源物。我们还认为 shugoshin 在真核生物中广泛保守。此外，我们还鉴定了 Sgo2，它是裂殖酵母中 shugoshin 的旁系同源物，它是忠实有丝分裂染色体分离所必需的。这些发现提供了对减数分裂的进化以及有丝分裂和减数分裂的动线调节的见解。