Talbert Paul B, Henikoff Steven
Howard Hughes Medical Institute, Fred Hutch Cancer Center, 1100 Fairview Avenue N, Seattle, WA, 98109, USA.
Chromosome Res. 2025 Aug 4;33(1):17. doi: 10.1007/s10577-025-09777-z.
The identification of CENPA, CENPB, and CENPC by Earnshaw and Rothfield 40 years ago has revealed the remarkable diversity and complexity of centromeres and confirmed most seed plants and animals have centromeres comprised of complex satellite arrays. The rapid evolution of centromeres and positive selection on CENPA and CENPC led to the centromere drive model, in which competition between tandem satellite arrays of differing size and centromere strength for inclusion in the egg of animals or megaspore of seed plants during female meiosis drives rapid evolution of centromeres and kinetochore proteins. Here we review recent work showing that non-B-form DNA structures in satellite centromeres make them sites of frequent replication fork stalling, and that repair of collapsed forks by break-induced replication rather than unequal sister chromatid exchange is likely the primary mode of satellite expansion and contraction, providing the variation in satellite copy number that is the raw material of centromere drive. Centromere breaks at replication, rather than errors at mitosis, can account for most centromere misdivisions that underlie aneuploidies in cancer.
40年前，恩肖（Earnshaw）和罗斯菲尔德（Rothfield）对着丝粒蛋白A（CENPA）、着丝粒蛋白B（CENPB）和着丝粒蛋白C（CENPC）的鉴定，揭示了着丝粒显著的多样性和复杂性，并证实大多数种子植物和动物的着丝粒由复杂的卫星阵列组成。着丝粒的快速进化以及对CENPA和CENPC的正选择导致了着丝粒驱动模型，即在雌性减数分裂过程中，不同大小和着丝粒强度的串联卫星阵列竞争进入动物卵子或种子植物大孢子，从而驱动着丝粒和动粒蛋白的快速进化。在这里，我们回顾了最近的研究工作，这些工作表明，卫星着丝粒中的非B型DNA结构使其成为复制叉频繁停滞的位点，并且通过断裂诱导复制而非不等姐妹染色单体交换来修复坍塌的复制叉可能是卫星扩张和收缩的主要模式，提供了作为着丝粒驱动原材料的卫星拷贝数变异。复制时的着丝粒断裂而非有丝分裂时的错误，可以解释大多数导致癌症非整倍体的着丝粒错误分裂。
