小柯机器人

美国国立卫生研究院NCI癌症研究中心Julia Promisel Cooper和Haitong Hou研究组合作取得一项新突破。他们发现基础减数分裂蛋白Spo11和Rec8可使中心粒解离。相关论文发表在2021年3月3日出版的《自然》杂志上。

他们显示了两个关键的减数分裂定义蛋白，拓扑异构酶Spo11（形成双链断裂）和减数分裂粘附素Rec8，可以使着丝粒解离。通常只有在缺乏端粒束的突变细胞中才能观察到这种解离，端粒束提供了有助于着丝粒重组的核微区。但是，Spo11或Rec8的过度表达会导致着丝粒的解离水平升高，而端粒束无法抵消。

特定的核小体重塑因子介导Spo11和Rec8的着丝粒解离。任一种蛋白在增殖细胞中的异位表达都会导致裂殖酵母和人类细胞中有丝分裂的动粒丢失。因此，尽管着丝粒染色质具有极高的稳定性，但Spo11和Rec8挑战了这种稳定性，并可能危及表达减数分裂蛋白的癌症中的动粒。

研究人员表示，减数分裂过程可能对基因组稳定性造成危险，如果在增殖细胞中被激活，则可能是灾难性的。

附：英文原文

Title: Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8

Author: Haitong Hou, Eftychia Kyriacou, Rahul Thadani, Michael Klutstein, Joseph H. Chapman, Julia Promisel Cooper

Issue&Volume: 2021-03-03

Abstract: Meiotic processes are potentially dangerous to genome stability and could be disastrous if activated in proliferative cells. Here we show that two key meiosis-defining proteins, the topoisomerase Spo11 (which forms double-strand breaks) and the meiotic cohesin Rec8, can dismantle centromeres. This dismantlement is normally observable only in mutant cells that lack the telomere bouquet, which provides a nuclear microdomain conducive to centromere reassembly1; however, overexpression of Spo11 or Rec8 leads to levels of centromere dismantlement that cannot be countered by the bouquet. Specific nucleosome remodelling factors mediate centromere dismantlement by Spo11 and Rec8. Ectopic expression of either protein in proliferating cells leads to the loss of mitotic kinetochores in both fission yeast and human cells. Hence, while centromeric chromatin has been characterized as extraordinarily stable, Spo11 and Rec8 challenge this stability and may jeopardize kinetochores in cancers that express meiotic proteins. The meiotic proteins Spo11 and Rec8, which ensure meiotic recombination and reductional chromosome segregation, have additional activities that challenge centromere stability by promoting centromeric nucleosome remodelling in both fission yeast and human cells.

DOI: 10.1038/s41586-021-03279-8

Source: https://www.nature.com/articles/s41586-021-03279-8

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