Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):10016-21. doi: 10.1073/pnas.1102106108. Epub 2011 May 26.
The mitotic checkpoint prevents a eukaryotic cell from commencing to separate its replicated genome into two daughter cells (anaphase) until all of its chromosomes are properly aligned on the metaphase plate, with the two copies of each chromosome attached to opposite poles of the mitotic spindle. The mitotic checkpoint is exquisitely sensitive in that a single unaligned chromosome, 1 of a total of ~50, is sufficient to delay progression into anaphase; however, when the last chromosome comes into alignment on the metaphase plate, the mitotic checkpoint is quickly satisfied, and the replicated chromosomes are rapidly partitioned to opposite poles of the dividing cell. The mitotic checkpoint is also curious in the sense that, before metaphase alignment, chromosomes that are not being pulled in opposite directions by the mitotic spindle activate the checkpoint, but during anaphase, these same tensionless chromosomes can no longer activate the checkpoint. These and other puzzles associated with the mitotic checkpoint are addressed by a proposed molecular mechanism, which involves two positive feedback loops that create a bistable response of the checkpoint to chromosomal tension.
有丝分裂检查点可防止真核细胞开始将其复制的基因组分离成两个子细胞（后期），直到其所有染色体都正确排列在中期板上，并且每条染色体的两个副本都附着在有丝分裂纺锤体的相对两极上。有丝分裂检查点非常敏感，即使只有一条未对齐的染色体（总共约 50 条染色体中的 1 条）也足以延迟进入后期；然而，当最后一条染色体在中期板上对齐时，有丝分裂检查点会迅速得到满足，复制的染色体迅速分配到分裂细胞的相对两极。有丝分裂检查点也很奇怪，因为在中期对齐之前，没有被有丝分裂纺锤体向相反方向拉动的染色体可以激活检查点，但在后期，这些没有张力的染色体就不能再激活检查点。通过提出的分子机制可以解决与有丝分裂检查点相关的这些和其他难题，该机制涉及两个正反馈回路，为检查点对染色体张力产生双稳态响应。
