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Diffusion and distal linkages govern interchromosomal dynamics during meiotic prophase
bioRxiv - Biophysics Pub Date : 2021-09-23 , DOI: 10.1101/2021.04.23.440859
Trent A. C. Newman , Bruno Beltran , James M. McGehee , Daniel Elnatan , Cori K. Cahoon , Michael R. Paddy , Daniel B. Chu , Andrew J. Spakowitz , Sean M. Burgess

The pairing of homologous chromosomes (homologs) in meiosis is essential for distributing the correct numbers of chromosomes into haploid gametes. In budding yeast, pairing depends on the formation of 150-200 Spo11-mediated double-strand breaks (DSBs) that are distributed among 16 homolog pairs, but it is not known if all, or only a subset of these DSBs, contribute to the close juxtaposition of homologs. Having established a system to measure the position of fluorescently tagged chromosomal loci in 3D space over time, we analyzed locus trajectories to determine how frequently, and how long, loci spend colocalized or apart. Continuous imaging revealed highly heterogeneous cell-to-cell behavior of foci, with the majority of cells exhibiting a “mixed” phenotype where foci move into and out of proximity, even at late stages of prophase, suggesting that the axial structures of the synaptonemal complex may be more dynamic than anticipated. The observed plateaus of the mean-squared change in distance (MSCD) between foci informed the development of a biophysical model of two diffusing polymers that captures the loss of centromere linkages as cells enter meiosis, nuclear confinement, and the formation of Spo11-dependent linkages. The predicted number of linkages per chromosome in our theoretical model closely approximates the small number (~2-4) of estimated synapsis-initiation sites, suggesting that excess DSBs have negligible effects on the overall juxtaposition of homologs. These insights into the dynamic in-terchromosomal behavior displayed during homolog pairing demonstrate the power of combining time-resolved in vivo analysis with modeling at the granular level.

中文翻译:

在减数分裂前期,扩散和远端联系控制着染色体间动力学

减数分裂中同源染色体(同源物)的配对对于将正确数量的染色体分配到单倍体配子中是必不可少的。在芽殖酵母中,配对取决于 150-200 个 Spo11 介导的双链断裂 (DSB) 的形成,这些双链断裂 (DSB) 分布在 16 个同源对中,但尚不清楚这些 DSB 是否全部或仅一部分有助于同系物的紧密并列。建立了一个系统来测量 3D 空间中荧光标记的染色体基因座的位置随时间推移,我们分析了基因座轨迹以确定基因座共定位或分开的频率和时间。连续成像揭示了病灶的高度异质性细胞间行为,大多数细胞表现出“混合”表型,其中病灶移入和移出邻近,即使在前期后期,这表明联会复合体的轴向结构可能比预期的更具动态性。观察到的病灶之间距离均方变化 (MSCD) 的平台期为两种扩散聚合物的生物物理模型的发展提供了信息. 在我们的理论模型中,预测的每条染色体的连接数非常接近估计的突触起始位点的少量(~2-4),这表明过量的 DSB 对同源物的整体并置的影响可以忽略不计。这些对同源配对期间显示的动态染色体间行为的见解证明了结合时间分辨的力量粒度级别建模的体内分析。
更新日期:2021-09-27
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