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Smc5/6 整体复合物对 DNA 片段的捕获

DNA segment capture by Smc5/6 holocomplexes.

机构信息

Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

出版信息

Nat Struct Mol Biol. 2023 May;30(5):619-628. doi: 10.1038/s41594-023-00956-2. Epub 2023 Apr 3.

DOI:10.1038/s41594-023-00956-2
PMID:37012407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10191858/
Abstract

Three distinct structural maintenance of chromosomes (SMC) complexes facilitate chromosome folding and segregation in eukaryotes, presumably by DNA loop extrusion. How SMCs interact with DNA to extrude loops is not well understood. Among the SMC complexes, Smc5/6 has dedicated roles in DNA repair and preventing a buildup of aberrant DNA junctions. In the present study, we describe the reconstitution of ATP-dependent DNA loading by yeast Smc5/6 rings. Loading strictly requires the Nse5/6 subcomplex which opens the kleisin neck gate. We show that plasmid molecules are topologically entrapped in the kleisin and two SMC subcompartments, but not in the full SMC compartment. This is explained by the SMC compartment holding a looped DNA segment and by kleisin locking it in place when passing between the two flanks of the loop for neck-gate closure. Related segment capture events may provide the power stroke in subsequent DNA extrusion steps, possibly also in other SMC complexes, thus providing a unifying principle for DNA loading and extrusion.

摘要

三种不同的结构维持染色体 (SMC) 复合物有助于真核生物的染色体折叠和分离，可能通过 DNA 环挤出实现。SMC 如何与 DNA 相互作用以挤出环尚不清楚。在 SMC 复合物中，Smc5/6 专门负责 DNA 修复和防止异常 DNA 连接点的积累。在本研究中，我们描述了酵母 Smc5/6 环的 ATP 依赖性 DNA 加载的重建。加载严格需要 Nse5/6 亚复合物，该亚复合物打开 kleisin 颈门。我们表明，质粒分子在 kleisin 和两个 SMC 亚复合物中被拓扑地困住，但不在完整的 SMC 隔室中。这可以通过 SMC 隔室持有一个环化的 DNA 片段来解释，并且当 kleisin 在环的两个侧翼之间通过以关闭颈门时，它将其锁定在适当的位置。相关的片段捕获事件可能为随后的 DNA 挤出步骤提供动力冲程，也可能在其他 SMC 复合物中提供，从而为 DNA 加载和挤出提供了一个统一的原则。

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