Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Institute for Research in Immunology and Cancer, University of Montreal, Montreal QC H3C 3J7, Canada.
Cell. 2013 Aug 29;154(5):1127-1139. doi: 10.1016/j.cell.2013.08.008.
Following DNA replication, eukaryotic cells must biorient all sister chromatids prior to cohesion cleavage at anaphase. In animal cells, sister chromatids gradually biorient during prometaphase, but current models of mitosis in S. cerevisiae assume that biorientation is established shortly after S phase. This assumption is based on the observation of a bilobed distribution of yeast kinetochores early in mitosis and suggests fundamental differences between yeast mitosis and mitosis in animal cells. By applying super-resolution imaging methods, we show that yeast and animal cells share the key property of gradual and stochastic chromosome biorientation. The characteristic bilobed distribution of yeast kinetochores, hitherto considered synonymous for biorientation, arises from kinetochores in mixed attachment states to microtubules, the length of which discriminates bioriented from syntelic attachments. Our results offer a revised view of mitotic progression in S. cerevisiae that augments the relevance of mechanistic information obtained in this powerful genetic system for mammalian mitosis.
在 DNA 复制后，真核细胞在后期姐妹染色单体分离前必须使所有姐妹染色单体正确取向。在动物细胞中，姐妹染色单体在前期逐渐正确取向，但 S. cerevisiae 有丝分裂的现有模型假设，在 S 期后不久就建立了正确取向。这一假设是基于在有丝分裂早期观察到酵母动粒的双叶状分布得出的，这表明酵母有丝分裂与动物细胞的有丝分裂存在根本差异。通过应用超分辨率成像方法，我们表明酵母和动物细胞具有逐渐和随机的染色体正确取向的关键特性。迄今被认为与正确取向同义的酵母动粒的特征性双叶状分布是由微管上附着状态混合的动粒引起的，微管的长度可区分正确取向的和联会附着。我们的结果提供了一个修订后的 S. cerevisiae 有丝分裂进展的观点，增加了在这个强大的遗传系统中获得的机制信息对哺乳动物有丝分裂的相关性。
