Identification And Characterization Of Human Rsc Chromat

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The ATP-dependent Chromatin-remodeling complex, Rsc, was originally identified in yeast. It has a subunit composition similar to the well-characterized 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 for the mitotic growth of yeast, whereas SWI/SNF is not. Rsc mutants are arrested at G2/M transition during the cell cycle, and the arrest is dependent on spindle-checkpoint genes. 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 that 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 (PMID: 11078522). 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.