在小鼠卵母细胞减数分裂过程中，着丝粒上的动态R环确保染色体排列，这一成果由中国科学院大学李伟研究团队经过不懈努力而取得。相关论文于2025年2月13日发表在《科学通报》杂志上。

本研究表明，在卵母细胞减数分裂过程中，R环及其调控因子RNase H1存在于着丝粒中。在中期I （MI）中，正确的着丝粒R环是确保卵母细胞染色体排列的必要条件。值得注意的是，卵母细胞中的Rnaseh1敲除和过表达都会导致严重的纺锤体组装缺陷和染色体错位，这是由于着丝粒上R环的失调。

此外，课题组研究人员发现复制蛋白A （RPA）被招募到着丝粒R环中，通过与ATR相互作用蛋白（ATRIP）相互作用，促进着丝粒上共济失调毛细血管扩张突变和Rad3相关（ATR）激酶的沉积。ATR激酶沉积触发CHK1的活性，刺激Aurora B的磷酸化，最终促进正常的纺锤体组装和染色体在赤道板的排列。最重要的是，应用ATR、CHK1和Aurora B抑制剂可以有效地修复卵母细胞中由于RNase H1缺乏而导致的纺锤体组装和染色体排列缺陷。

总的来说，他们的发现揭示了R环在母细胞减数分裂过程中的关键作用，表明R环的失调可能与女性不育有关。此外，ATR、CHK1和Aurora B抑制剂可能被用于治疗一些不孕症患者。

据了解，R环在许多生理过程中发挥着不同的作用，然而，它们在减数分裂中的作用在很大程度上仍然未知。

附：英文原文

Title: Dynamic R-loops at centromeres ensure chromosome alignment during oocyte meiotic divisions in mice

Author: Meijia Zhang e, Fei Gao b c, Chao Liu a b c, Wei Li a b c

Issue&Volume: 2025/02/13

Abstract: R-loops play various roles in many physiological processes, however, their role in meiotic division remains largely unknown. Here we show that R-loops and their regulator RNase H1 are present at centromeres during oocyte meiotic divisions. Proper centromeric R-loops are essential to ensure chromosome alignment in oocytes during metaphase I (MI). Remarkably, both Rnaseh1 knockout and overexpression in oocytes lead to severe spindle assembly defects and chromosome misalignment due to dysregulation of R-loops at centromeres. Furthermore, we find that replication protein A (RPA) is recruited to centromeric R-loops, facilitating the deposition of ataxia telangiectasia-mutated and Rad3-related (ATR) kinase at centromeres by interacting with the ATR-interaction protein (ATRIP). The ATR kinase deposition triggers the activity of CHK1, stimulating the phosphorylation of Aurora B to finally promote proper spindle assembly and chromosome alignment at the equatorial plate. Most importantly, the application of ATR, CHK1, and Aurora B inhibitors could efficiently rescue the defects in spindle assembly and chromosome alignment due to RNase H1 deficiency in oocytes. Overall, our findings uncover a critical role of R-loops during mouse oocyte meiotic divisions, suggesting that dysregulation of R-loops may be associated with female infertility. Additionally, ATR, CHK1, and Aurora B inhibitors may potentially be used to treat some infertile patients.

DOI: 10.1016/j.scib.2025.02.009

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927325001689