The people in my laboratory study how chromosomes which contain genetic information, move during cell division. Chromosome movement at mitosis is mediated by a specialized region of each chromosome called the centromere which interacts with the microtubules of the mitotic spindle. The focus of our research is directed at characterizing the DNA and proteins required for centromere function. We chose the yeast, Saccharomyces cerevisiae, as our model organism because this single-cell eucaryote divides rapidly and has well-characterized centromere DNA (CEN) and a relatively simple kinetochore structure. Yeast are amenable to a wide array of methodologies ranging from classical genetics to advanced recombinant DNA and biochemical techniques. In addition, the entire yeast genome has been sequenced, which has provided important genetic information and led to the identification of many yeast/human homologs.

We have devised genetic screens to identify proteins involved in centromere function and chromosome segregation. These screens have yielded several novel genes (CSE1, SRP1, PLC1), including the current focus of our work, CSE4. The essential gene CSE4 encodes a chromatin-associated protein with striking homology to histone H3 and the human centromere protein, CENP-A. We have constructed a wide array of mutations in the CSE4 protein (Cse4p) and have identified several other genes required for Cse4p function. These data indicate that Cse4p plays an important role in centromere function and cell cycle control. Currently, genetic and biochemical experiments are under way to analyze function when Cse4p replaces H3 in an evolutionarily conserved, specialized chromatin domain that is required for function of the eucaryotic centromere.

BIOCHM/MCBIO 642: Advanced Molecular and Cellular Biology
BIOCHM 491H: Honors Seminar
BIOCHM XXX: My DNA