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。它的亚基组成类似于SWI/SNF：两个复合体共享两个亚基，至少还有4个亚基是彼此的同系物。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，并且这种阻止依赖于纺锤体-检查点基因。突变体对破坏微管稳定的药物也更敏感。这些数据表明，RSC可能在有丝分裂中发挥作用，可能是通过稳定有丝分裂纺锤体的形成或在动粒上起作用。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，我们现在鉴定了人SWI/SNF-B复合体的BAF180亚基是酵母RSC亚基Rsc1、Rsc2和Rsc4的人类同源物。它与RSC的3个亚基具有相同的生化基序：6个溴区、2个BAH区和一个小槽结合区。对完整的人、果蝇和优雅果蝇的基因组数据库进行数据库搜索，结果表明BAF180是三个RSC亚基中最接近的同源基因，这表明人类SWI/SNF-B是RSC的人类版本。我们随后鉴定了人类RSC复合体的许多其他亚基，并发现其中一些亚基与人类SWI/SNF中的亚基相同。我们还证明了BAF180定位于有丝分裂染色体的着丝点，与RSC在有丝分裂过程中的功能一致。这项研究最近发表在《美国国家科学院院刊》上(薛等人，2000年第97卷：13105页)。我们目前正在努力确定人类SWI/SNF-B的剩余成分。未来，我们将努力识别受这种复合体调控的基因。

The ATP-dependent Chromatin-remodeling complex, Rsc, was originally identified in yeast. It has a subunit composition similar to 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 the arrest is dependent on the spindle- checkpoint gene. The mutants 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 or have a function at kinetochores. 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 the BAF180 subunit of human SWI/SNF-B complex as a human homologue of yeast Rsc subunits, Rsc1, Rsc2 and Rsc4. It has the same set of biochemical motifs as the three Rsc subunits: 6 bromodomains, 2 BAH regions, and a minor-groove binding domain. Database search of the completed genome database of human, Drosophila and C.elegance showed that BAF180 is the closest homolog of the three Rsc subunits, suggesting human SWI/SNF-B as a human version of Rsc. We subsequently identified many other subunits of human Rsc complex and found a number of them to be identical to those in human SWI/SNF. We also demonstrated that BAF180 localizes at kinetochores of mitotic chromosomes, consistent with a function for Rsc during mitosis. This work has recently been published in PNAS (Xue et al., Vol 97:13105, 2000). We are currently trying to identify the remaining components of human SWI/SNF-B. In the future, we will try to identify genes that are regulated by this complex.