Gene Expression, Cell Cycle & Chromosome Biology
Defective replication initiation results in locus specific chromosome breakage and a ribosome deficiency in budding yeast
My long-term interest is to understand how mutations in DNA replication machinery affect human health. My current research is focused on studying mutations associated with a rare form of primordial dwarfism called Meier-Gorlin Syndrome (MGS). Because these mutations occur in highly conserved regions of replication initiation proteins between humans and yeast, I am using yeast to examine how these mutations affect phenotypes on a cellular and molecular level. I have found several interesting phenotypes in MGS yeast, one of which is a large reduction in ribosomal DNA repeats. Different models have been proposed to explain this phenotype and I am in the process of testing them. My goal is that insight gained from studying conserved MGS mutations in yeast will provide a better understanding to the phenotypes observed in humans.