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DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes

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Meiotic chromosome pairing, recombination, and fertility depends on the conserved loop-axis architecture of meiotic chromosomes. This architecture is modulated by condensin, a structural maintenance of chromosome (SMC) complex that catalyzes chromatin loop formation. Here, we investigated how condensin is recruited to meiotic chromosomes in Saccharomyces cerevisiae. We show that double-strand break (DSB) formation, the initiating event of meiotic recombination, causes condensin redistribution from the nucleolus to DSB hotspots, pericentromeric regions and axis attachment sites. Hotspot association of condensin correlates weakly with break probability but does not depend on local DSB formation, whereas association with axis sites and pericentromeric regions depends on the Scc2-associated pool of cohesin, another SMC complex. Intriguingly, Scc2 distribution also changes in response to DSB formation. As condensin and Scc2-cohesin both catalyze chromatin loop extrusion, their redistribution upon DSB formation implies a profound change in chromatin loop dynamics that may help promote proper chromosome pairing and DNA repair.

减数分裂染色体配对、重组与育性依赖于减数分裂染色体保守的环轴结构。该结构由凝缩蛋白(condensin)调控——凝缩蛋白是一类催化染色质环形成的染色体结构维持(SMC)复合物。本研究以酿酒酵母(Saccharomyces cerevisiae)为实验材料,探究了凝缩蛋白向减数分裂染色体的招募机制。研究发现,作为减数分裂重组起始事件的双链断裂(DSB)形成,会促使凝缩蛋白从核仁重新分布至DSB热点、着丝粒周边区域及轴附着位点。凝缩蛋白与DSB热点的结合仅与断裂概率呈弱相关,且不依赖于局部DSB的形成;而其与轴位点及着丝粒周边区域的结合,则依赖于另一SMC复合物——结合Scc2的黏连蛋白(cohesin)库。值得注意的是,Scc2的分布同样会随DSB形成发生改变。鉴于凝缩蛋白与Scc2关联的黏连蛋白均能催化染色质环挤压,二者在DSB形成后的重新分布,意味着染色质环动态性发生了显著改变,这或有助于促进染色体的正确配对与DNA修复。

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