Identification and Characterization of human Rsc Chromatin-Remodeling Complex

依赖于三磷酸腺苷的染色质重塑复合体RSC最初是在酵母中发现的。它的亚基组成与SWI/SNF相似：两个复合体共享两个亚基，至少还有4个亚基是彼此的同源物。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突变体被阻止在G2/M转换，这种阻止依赖于纺锤体-检查点基因。他们对破坏微管稳定的药物也更敏感。这些数据表明，RSC可能通过稳定有丝分裂纺锤体的形成而在有丝分裂中发挥作用。我们之前已经从人类中纯化了几个依赖于ATP的染色质重塑复合体，它们与酵母SWI/SNF或RSC密切相关。通过微测序和克隆，我们现在鉴定出特定复合体的一个亚基是酵母RSC亚基Rsc1和Rsc2的人类同源物。我们随后鉴定了人类RSC复合体的许多其他亚基，并发现许多亚基与人类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一部分的机制。

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.