Patrick A. Grant, PhD
Covalent histone modifications and deregulation in cancer
The regulated expression of genetic material is a crucial step in the normal development and maintenance of life in organisms as divergent as yeast and humans. The post-translation modification of the histone components of chromatin is postulated to play a central role in this process, but also in the etiology of viral infection and cancer. Misregulation of chromatin structure can cause incorrect gene activation or improper gene silencing. Thus, an organized pattern of acetylation, methylation and phosphorylation of chromatin in the normal regulation of gene expression and cell cycle progression. The Grant lab studies are directed at understanding how conserved histone modifications and the enzymatic complexes that generate them regulate DNA-templated events such as transcription, repair and replication. In particular their studies involve the functions of native yeast SAGA and SLIK (SAGA-Like), histone acetyltransferase/ coactivator complexes, which have been remarkably maintained through evolution. A better understanding of how chromatin modifying factors function has proven to be vital for them to generate a clear picture of how genes may be regulated in health and disease. Furthermore, they are investigating how chromatin modification is regulated in response to DNA damage by these and other complexes. Specifically they are conducting studies into how chromatin remodeling factors respond to potentially cancerous and cytotoxic lesions caused by UV damage or double strand breaks. For example they have initiated a study into how the protein CDC7, overexpressed in certain cancer cells, promotes error prone DNA replication.