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小鼠染色体刚度的细胞周期及与年龄相关的调节

Cell cycle and Age-Related Modulations of Mouse Chromosome Stiffness.

作者信息

Liu Ning, Qiang Wenan, Jordan Philip, Marko John F, Qiao Huanyu

机构信息

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Center for Developmental Therapeutics, Northwestern University, Evanston, IL, USA.

出版信息

bioRxiv. 2025 Mar 10:2024.03.06.583771. doi: 10.1101/2024.03.06.583771.

Abstract

Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a ten-fold increase in stiffness (Young's modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle, and by age-related factors.

摘要

染色体结构复杂,染色体组织的许多方面仍不为人所知。测量染色体的刚度能为其结构特性提供有价值的见解。在本研究中,我们分析了减数第一次分裂中期(MI)和减数第二次分裂中期(MII)卵母细胞染色体的刚度。我们的结果显示,与体细胞染色体相比,MI染色体的刚度(杨氏模量)增加了十倍。此外,发现MII染色体的刚度低于MI染色体。我们研究了减数分裂特异性黏连蛋白复合体在调节染色体刚度中的作用。令人惊讶的是,来自三个减数分裂特异性黏连蛋白突变体的染色体刚度与野生型染色体的刚度没有显著差异,这表明这些黏连蛋白可能不是染色体刚度的主要决定因素。此外,我们的研究结果显示,MI卵母细胞的染色体刚度随年龄增长而增加。由于衰老与DNA损伤水平升高有关,我们研究了依托泊苷诱导的DNA损伤对染色体刚度的影响,发现它导致MI卵母细胞的刚度降低。总体而言,我们的研究强调了染色体刚度的动态和周期性本质,它受到细胞周期和与年龄相关因素的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/306b65657a65/nihpp-2024.03.06.583771v3-f0001.jpg

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