Tong Ze-Bin, Ai Hua-Song, Li Jia-Bin
College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, China.
Front Cell Dev Biol. 2020 Sep 25;8:560098. doi: 10.3389/fcell.2020.560098. eCollection 2020.
DNA packs into highly condensed chromatin to organize the genome in eukaryotes but occludes many regulatory DNA elements. Access to DNA within nucleosomes is therefore required for a variety of biological processes in cells including transcription, replication, and DNA repair. To cope with this problem, cells employ a set of specialized ATP-dependent chromatin-remodeling protein complexes to enable dynamic access to packaged DNA. In the present review, we summarize the recent advances in the functional and mechanistic studies on a particular chromatin remodeler SMARCAD1 which has been demonstrated to play a key role in distinct cellular processes and gained much attention in recent years. Focus is given to how SMARCAD1 regulates various cellular processes through its chromatin remodeling activity, and especially the regulatory role of SMARCAD1 in gene expression control, maintenance and establishment of heterochromatin, and DNA damage repair. Moreover, we review the studies on the molecular mechanism of SMARCAD1 that promotes the DNA end-resection on double-strand break ends, including the mechanisms of recruitment, activity regulation and chromatin remodeling.
在真核生物中，DNA 包装成高度浓缩的染色质以组织基因组，但会封闭许多调控性 DNA 元件。因此，细胞内的各种生物学过程，包括转录、复制和 DNA 修复，都需要能够接触核小体内的 DNA。为了解决这个问题，细胞利用一组专门的依赖 ATP 的染色质重塑蛋白复合物，以实现对包装好的 DNA 的动态接触。在本综述中，我们总结了对一种特定染色质重塑因子 SMARCAD1 的功能和机制研究的最新进展，该因子已被证明在不同的细胞过程中起关键作用，近年来备受关注。重点关注 SMARCAD1 如何通过其染色质重塑活性调节各种细胞过程，特别是 SMARCAD1 在基因表达控制、异染色质的维持和建立以及 DNA 损伤修复中的调控作用。此外，我们回顾了关于 SMARCAD1 促进双链断裂末端 DNA 末端切除的分子机制的研究，包括招募、活性调节和染色质重塑的机制。
