Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India.
PLoS Genet. 2023 Oct 9;19(10):e1010986. doi: 10.1371/journal.pgen.1010986. eCollection 2023 Oct.
Extra-chromosomal selfish DNA elements can evade the risk of being lost at every generation by behaving as chromosome appendages, thereby ensuring high fidelity segregation and stable persistence in host cell populations. The yeast 2-micron plasmid and episomes of the mammalian gammaherpes and papilloma viruses that tether to chromosomes and segregate by hitchhiking on them exemplify this strategy. We document for the first time the utilization of a SWI/SNF-type chromatin remodeling complex as a conduit for chromosome association by a selfish element. One principal mechanism for chromosome tethering by the 2-micron plasmid is the bridging interaction of the plasmid partitioning proteins (Rep1 and Rep2) with the yeast RSC2 complex and the plasmid partitioning locus STB. We substantiate this model by multiple lines of evidence derived from genomics, cell biology and interaction analyses. We describe a Rep-STB bypass system in which a plasmid engineered to non-covalently associate with the RSC complex mimics segregation by chromosome hitchhiking. Given the ubiquitous prevalence of SWI/SNF family chromatin remodeling complexes among eukaryotes, it is likely that the 2-micron plasmid paradigm or analogous ones will be encountered among other eukaryotic selfish elements.
染色体外自私 DNA 元件可以通过作为染色体附属物来逃避每一代丢失的风险，从而确保在宿主细胞群体中具有高保真度的分离和稳定的持久性。酵母 2μm 质粒和哺乳动物 γ 疱疹病毒和乳头瘤病毒的外源性染色体通过搭便车分离，就是这种策略的范例。我们首次记录了自私元件利用 SWI/SNF 型染色质重塑复合物作为与染色体关联的通道。2μm 质粒通过与酵母 RSC2 复合物和质粒分配位点 STB 的质粒分配蛋白（Rep1 和 Rep2）的桥接相互作用来固定染色体的主要机制。我们通过来自基因组学、细胞生物学和相互作用分析的多个证据来证实这个模型。我们描述了一种 Rep-STB 旁路系统，其中一种设计为与 RSC 复合物非共价结合的质粒通过染色体搭便车来模拟分离。鉴于 SWI/SNF 家族染色质重塑复合物在真核生物中的普遍存在，2μm 质粒范例或类似范例很可能会在其他真核自私元件中遇到。
