Analysis of the regulation of meiosis-specific chromosome segregation

在有丝分裂过程中，姐妹着丝点附着在微管上，微管延伸到相对的纺锤体极，并在后期将染色单体拉开(平衡分离)。一种称为粘附素的多亚单位复合体，包括Rad21/Scc1，在姐妹染色单体凝聚和有丝分裂等式分离中起着至关重要的作用。减数分裂I与有丝分裂的不同之处在于染色体分离的简化模式，即姐妹着丝点附着在同一纺锤体上。在减数分裂过程中，Rad21/Scc1在很大程度上被其对应的减数分裂产物Rec8所取代。如果Rec8在分裂酵母中失活，减数分裂I就从还原分裂转变为等分分裂。然而，REC8Δ细胞经历等式分裂而不是随机分裂的原因尚不清楚。在这里，我们已经证明了减数分裂I的平衡分离取决于取代基Rad21，如果没有Rec8，它就会重新定位到着丝粒。因此，在分裂酵母的减数分裂I期，粘附素是动丝点与纺锤体微管附着方式的关键决定因素。众所周知，姐妹染色单体凝聚力必须在第一次减数分裂(减数分裂I)的着丝粒上持续存在，此时只有手臂凝聚力被破坏。在减数分裂过程中保护着丝粒凝聚力的因素一直是难以捉摸的。在这里，我们鉴定了Sgo1(Shugoshin)，它是分裂酵母中着丝粒Rec8粘附素的保护者，也是萌芽酵母中的同源物。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，这是分裂酵母中舒戈申蛋白的一种类似物，它是有丝分裂染色体分离所必需的。这些发现为有丝分裂和减数分裂的减数分裂和动粒调控的进化提供了洞察力。

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.