Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Mol Cell Biol. 2010 Jan;30(2):537-49. doi: 10.1128/MCB.00980-09. Epub 2009 Nov 16.
It has been firmly established that many interphase nuclear functions, including transcriptional regulation, are regulated by chromatin and histones. How mitotic progression and quality control might be influenced by histones is less well characterized. We show that histone H3 plays a crucial role in activating the spindle assembly checkpoint in response to a defect in mitosis. Prior to anaphase, all chromosomes must attach to spindles emanating from the opposite spindle pole bodies. The tension between sister chromatids generated by the poleward pulling force is an integral part of chromosome biorientation. Lack of tension due to erroneous attachment activates the spindle assembly checkpoint, which corrects the mistakes and ensures segregation fidelity. A histone H3 mutation impairs the ability of yeast cells to activate the checkpoint in a tensionless crisis, leading to missegregation and aneuploidy. The defects in tension sensing result directly from an attenuated H3-Sgo1p interaction essential for pericentric recruitment of Sgo1p. Reinstating the pericentric enrichment of Sgo1p alleviates the mitotic defects. Histone H3, and hence the chromatin, is thus a key factor transmitting the tension status to the spindle assembly checkpoint.
已经明确，许多核内相功能，包括转录调控，都受到染色质和组蛋白的调节。有丝分裂进程和质量控制如何受到组蛋白的影响还不太清楚。我们发现组蛋白 H3 在有丝分裂缺陷时激活纺锤体组装检查点方面起着关键作用。在后期开始之前，所有染色体都必须附着到从相对纺锤体极体发出的纺锤体上。姐妹染色单体之间由向极拉力产生的张力是染色体双定向的一个组成部分。由于错误连接导致的张力缺失会激活纺锤体组装检查点，该检查点会纠正错误并确保分离保真度。组蛋白 H3 的突变会损害酵母细胞在无张力危机中激活检查点的能力，导致染色体错误分离和非整倍体。张力感测缺陷直接源于 H3-Sgo1p 相互作用的减弱，这对于 Sgo1p 着丝粒募集至关重要。恢复 Sgo1p 的着丝粒富集可缓解有丝分裂缺陷。因此，组蛋白 H3 及其染色质是将张力状态传递给纺锤体组装检查点的关键因素。
