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Structure of a dimer of the Sulfolobus solfataricus MCM N-terminal domain reveals a potential role in MCM ring opening
Acta Crystallographica Section F ( IF 1.1 ) Pub Date : 2021-06-02 , DOI: 10.1107/s2053230x21005331
Martin Meagher 1 , Madison N Spence 1 , Eric J Enemark 1
Affiliation  

Cells strongly regulate DNA replication to ensure genomic stability and prevent several diseases, including cancers. Eukaryotes and archaea strictly control DNA-replication initiation by the regulated loading of hexameric minichromosome maintenance (MCM) rings to encircle both strands of the DNA double helix followed by regulated activation of the loaded rings such that they then encircle one DNA strand while excluding the other. Both steps involve an open/closed ring transformation, allowing DNA strands to enter or exit. Here, the crystal structure of a dimer of the N-terminal domain of Sulfolobus solfataricus MCM with an intersubunit interface that is more extensive than in closed-ring structures, while including common interactions to enable facile interconversion, is presented. It is shown that the identified interface could stabilize open MCM rings by compensating for lost interactions at an open neighbor interface and that the prior open-ring cryo-EM structure of MCM loading has a similar extended interface adjacent to its open interface.

中文翻译:

硫磺硫化叶菌 MCM N 末端结构域二聚体的结构揭示了 MCM 开环中的潜在作用

细胞强烈调节 DNA 复制,以确保基因组稳定性并预防多种疾病,包括癌症。真核生物和古细菌通过调节六聚体微型染色体维持 (MCM) 环的加载来严格控制 DNA 复制起始,以包围 DNA 双螺旋的两条链,然后调节加载的环的激活,使它们包围一条 DNA 链,同时排除另一条 DNA 链。这两个步骤都涉及开环/闭环转换,允许 DNA 链进入或退出。在这里,介绍了硫磺硫化叶菌 MCM N 端结构域二聚体的晶体结构,其亚基间界面比闭环结构更广泛,同时包括常见的相互作用以实现轻松的相互转化。结果表明,所识别的界面可以通过补偿开放相邻界面处丢失的相互作用来稳定开放MCM环,并且MCM加载的先前开环冷冻电镜结构具有与其开放界面相邻的类似扩展界面。
更新日期:2021-06-08
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