de Wolf Bas, Kops Geert J P L
Hubrecht Institute - KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands.
Adv Exp Med Biol. 2017;1002:69-91. doi: 10.1007/978-3-319-57127-0_4.
The cell cycle culminates in mitosis with the purpose of dividing the cell's DNA content equally over two daughter cells. Error-free segregation relies on correct connections between chromosomes and spindle microtubules. Kinetochores are complex multi-protein assemblies that mediate these connections and are the platforms for attachment-error-correction and spindle assembly checkpoint signaling. Proper kinetochore function is therefore key in preventing aneuploidization. Mutations in genes encoding kinetochore proteins are associated with several severe developmental disorders associated with microcephaly, and kinetochore defects contribute to chromosomal instability in certain cancers. This chapter gives an overview of the processes necessary for faithful chromosome segregation and how kinetochore malfunction causes various human pathologies.
细胞周期以有丝分裂告终，目的是将细胞的DNA含量平均分配到两个子细胞中。无差错分离依赖于染色体与纺锤体微管之间的正确连接。动粒是介导这些连接的复杂多蛋白组装体，是附着错误校正和纺锤体组装检查点信号传导的平台。因此，正确的动粒功能是防止非整倍体形成的关键。编码动粒蛋白的基因突变与几种与小头畸形相关的严重发育障碍有关，动粒缺陷在某些癌症中导致染色体不稳定。本章概述了准确的染色体分离所需的过程，以及动粒功能异常如何导致各种人类疾病。
