Functional and structural studies of chromatin remodeling

Processes of DNA metabolism require that factors gain access to cis regulatory elements on the DNA template, however, the packaging of DNA into chromatin often renders these sites inaccessible. A dynamic chromatin structure is established through the activities of two classes of chromatin remodelers: the ATP-dependent chromatin remodelers and the histone acetyltransferases (HATs). These complexes are conserved in all eukaryotes, and defects in the activities of the chromatin remodelers often result in cancer. To better understand these remarkable classes of factors, we study the ATP-dependent chromatin remodeler, RSC. RSC contains several novel polypeptides that may serve as targeting molecules. We have used the zinc cluster proteins Rsc3 and Rsc30 to better understand the processes of targeting and the cellular roles of the RSC complex. Further, to begin to understand the substrate specificity of histone acetyltransferases, we have determined the structure of the Hpa2 tetramer in complex with acetyl coenzyme A.