Principal Investigator Natalie Kuldell
Large protein complexes regulate eukaryotic gene expression by modifying the nucleosomes that package DNA into chromatin. One such chromatin-modifying complex, SAGA, is functionally conserved in other eukaryotic cells. Given the notable but limited sequence conservation of its subunits, its modular nature and its critical role in gene expression, SAGA is an attractive engineering platform. My aim is to develop a generic SAGA complex that can function in a wide variety of cell types, from yeast to flies to human. As a first step to such a useful complex, I have swapped nonessential subunits of the S. cerevisiae complex with their homologs from S. pombe, an evolutionarily distant yeast species. Phenotypes associated with the subunit deletions and replacements are being explored as they may give insight into the natural function of the SAGA complex and help define the constraints for its modification.