Identification and Characterization of human Rsc Chromatin-Remodeling Complex

人类 Rsc 染色质重塑复合物的鉴定和表征

• 批准号: 6431445
• 负责人: Weidong Wang
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431445
• 关键词: adenosine triphosphate; cell cycle; cell cycle proteins; chromatin; microtubules; mitotic spindle apparatus; molecular cloning; mutant; nucleic acid sequence; tissue /cell culture

The ATP-dependent Chromatin-remodeling complex, Rsc, was originally identified in yeast. It has similar subunit composition as SWI/SNF: 2 subunits are shared between the two complexes and at least 4 others are homologues of each other. However, the function of Rsc is distinct from SWI/SNF. Rsc is essential to the mitotic growth of yeast, whereas SWI/SNF is not. The rsc mutants are arrested at G2/M transition during the cell cycle and this arrest is dependent on the spindle-checkpoint gene. They are also more sensitive to microtubule-destabilizing drugs. These data suggest that Rsc may play a role in mitosis perhaps by stabilizing mitotic spindle formation. We have previously purified several ATP-dependent chromatin remodeling complexes from human which are closely-related to either yeast SWI/SNF or Rsc. By microsequencing and cloning, we now identified one subunit of a particular complex as a human homologue of yeast Rsc subunits, Rsc1 and Rsc2. We subsequently identified many other subunits of human Rsc complex and found many of them to be identical to those in human SWI/SNF. Preliminary data suggest that human Rsc may directly participate in mitosis by binding to microtubules. We are continuing to investigate this part of the mechanism.

ATP依赖性染色质重塑复合物Rsc最初在酵母中鉴定。它具有与SWI/SNF相似的亚基组成：两个复合物之间共享2个亚基，并且至少4个其他亚基彼此同源。然而，Rsc的功能不同于SWI/SNF。Rsc对酵母的有丝分裂生长是必需的，而SWI/SNF不是。在细胞周期中，rsc突变体在G2/M转换时被阻滞，并且这种阻滞依赖于纺锤体检查点基因。它们对微管不稳定药物也更敏感。这些数据表明，Rsc可能在有丝分裂中发挥作用，可能通过稳定有丝分裂纺锤体的形成。我们以前从人中纯化了几种ATP依赖的染色质重塑复合物，它们与酵母SWI/SNF或Rsc密切相关。通过微测序和克隆，我们现在确定了一个特定复合物的一个亚基作为酵母Rsc亚基Rsc 1和Rsc 2的人类同源物。我们随后鉴定了人Rsc复合物的许多其他亚基，并发现其中许多亚基与人SWI/SNF中的亚基相同。初步数据表明，人Rsc可能通过与微管结合直接参与有丝分裂。我们正在继续调查这部分机制。