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黏合蛋白环建立 DNA-DNA 相互作用。

Establishment of DNA-DNA Interactions by the Cohesin Ring.

机构信息

Institute of Innovative Research, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.

Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

出版信息

Cell. 2018 Jan 25;172(3):465-477.e15. doi: 10.1016/j.cell.2017.12.021. Epub 2018 Jan 18.

Abstract

The ring-shaped structural maintenance of chromosome (SMC) complexes are multi-subunit ATPases that topologically encircle DNA. SMC rings make vital contributions to numerous chromosomal functions, including mitotic chromosome condensation, sister chromatid cohesion, DNA repair, and transcriptional regulation. They are thought to do so by establishing interactions between more than one DNA. Here, we demonstrate DNA-DNA tethering by the purified fission yeast cohesin complex. DNA-bound cohesin efficiently and topologically captures a second DNA, but only if that is single-stranded DNA (ssDNA). Like initial double-stranded DNA (dsDNA) embrace, second ssDNA capture is ATP-dependent, and it strictly requires the cohesin loader complex. Second-ssDNA capture is relatively labile but is converted into stable dsDNA-dsDNA cohesion through DNA synthesis. Our study illustrates second-DNA capture by an SMC complex and provides a molecular model for the establishment of sister chromatid cohesion.

摘要

环状结构维持染色体(SMC)复合物是多亚基 ATP 酶,可使 DNA 拓扑环绕。SMC 环对许多染色体功能做出了重要贡献,包括有丝分裂染色体浓缩、姐妹染色单体黏合、DNA 修复和转录调控。它们通过在一个以上的 DNA 之间建立相互作用来实现这一点。在这里,我们通过纯化的裂殖酵母黏合复合物证明了 DNA-DNA 连接。结合 DNA 的黏合复合物有效地、拓扑地捕获第二个 DNA,但前提是该 DNA 是单链 DNA(ssDNA)。与初始双链 DNA(dsDNA)的结合类似,第二个 ssDNA 的捕获依赖于 ATP,并且严格需要黏合复合物加载器。第二个 ssDNA 的捕获相对不稳定,但通过 DNA 合成转化为稳定的 dsDNA-dsDNA 黏合。我们的研究说明了 SMC 复合物对第二个 DNA 的捕获,并提供了姐妹染色单体黏合建立的分子模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7d4/5786502/ed9928ab3bca/fx1.jpg

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