Ottawa Institute of Systems Biology, Department of Cellular and Molecular Medicine, University of Ottawa, Roger Guindon Hall, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada.
Nucleic Acids Res. 2024 Mar 21;52(5):2112-2129. doi: 10.1093/nar/gkae103.
High-level folding of chromatin is a key determinant of the shape and functional state of chromosomes. During cell division, structural maintenance of chromosome (SMC) complexes such as condensin and cohesin ensure large-scale folding of chromatin into visible chromosomes. In contrast, the SMC5/6 complex plays more local and context-specific roles in the structural organization of interphase chromosomes with important implications for health and disease. Recent advances in single-molecule biophysics and cryo-electron microscopy revealed key insights into the architecture of the SMC5/6 complex and how interactions connecting the complex to chromatin components give rise to its unique repertoire of interphase functions. In this review, we provide an integrative view of the features that differentiates the SMC5/6 complex from other SMC enzymes and how these enable dramatic reorganization of DNA folding in space during DNA repair reactions and other genome transactions. Finally, we explore the mechanistic basis for the dynamic targeting of the SMC5/6 complex to damaged chromatin and its crucial role in human health.
染色质的高级折叠是染色体形态和功能状态的关键决定因素。在细胞分裂过程中，结构维持染色体（SMC）复合物，如凝聚素和黏合素，确保了染色质的大规模折叠成可见的染色体。相比之下，SMC5/6 复合物在有丝分裂染色体的结构组织中发挥更局部和特定于上下文的作用，对健康和疾病具有重要意义。单分子生物物理学和冷冻电子显微镜的最新进展揭示了 SMC5/6 复合物的结构以及连接复合物与染色质成分的相互作用如何产生其独特的有丝分裂功能的关键见解。在这篇综述中，我们提供了一个综合的观点，即区分 SMC5/6 复合物与其他 SMC 酶的特征，以及这些特征如何使 DNA 修复反应和其他基因组转导过程中 DNA 折叠在空间上发生剧烈的重排。最后，我们探讨了 SMC5/6 复合物动态靶向受损染色质的机制基础及其在人类健康中的关键作用。
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