Biophysics and Mechanobiology Laboratory, The Francis Crick Institute, London, UK.
Chromosome Segregation Laboratory, The Francis Crick Institute, London, UK.
Nat Struct Mol Biol. 2024 Jan;31(1):23-31. doi: 10.1038/s41594-023-01122-4. Epub 2023 Oct 23.
Cohesin forms a proteinaceous ring that is thought to link sister chromatids by entrapping DNA and counteracting the forces generated by the mitotic spindle. Whether individual cohesins encircle both sister DNAs and how cohesin opposes spindle-generated forces remains unknown. Here we perform force measurements on individual yeast cohesin complexes either bound to DNA or holding together two DNAs. By covalently closing the hinge and Smc3-kleisin interfaces we find that the mechanical stability of the cohesin ring entrapping DNA is determined by the hinge domain. Forces of ~20 pN disengage cohesin at the hinge and release DNA, indicating that ~40 cohesin molecules are sufficient to counteract known spindle forces. Our findings provide a mechanical framework for understanding how cohesin interacts with sister chromatids and opposes the spindle-generated tension during mitosis, with implications for other force-generating chromosomal processes including transcription and DNA replication.
着丝粒蛋白形成一个蛋白环，通过捕获 DNA 并对抗有丝分裂纺锤体产生的力来连接姐妹染色单体。单个着丝粒蛋白是否环绕两个姐妹 DNA 以及着丝粒蛋白如何对抗纺锤体产生的力尚不清楚。在这里，我们对结合 DNA 的单个酵母着丝粒复合物或连接两个 DNA 的复合物进行力测量。通过共价闭合铰链和 Smc3-klisin 界面，我们发现，束缚 DNA 的着丝粒环的机械稳定性由铰链结构域决定。在铰链处，约 20 pN 的力使着丝粒蛋白脱离，并释放 DNA，表明大约 40 个着丝粒蛋白足以对抗已知的纺锤体力。我们的发现为理解着丝粒如何与姐妹染色单体相互作用以及在有丝分裂过程中如何对抗纺锤体产生的张力提供了一个机械框架，这对包括转录和 DNA 复制在内的其他产生力的染色体过程具有重要意义。
