At a glance:
- The organization and distribution of chromosomes when cells divide.
- Building artificial chromosomes to study how they work.
- Introduction of chromosomes into living cells, providing a means of assessing their functionality. Through these studies we are starting to gain significant insights into how chromosomes are organized and the mechanisms responsible for chromosome distribution during the life of a cell.
Our laboratory is interested in the mechanisms of chromosome segregation. Chromosomes have been constructed by recombinant DNA techniques and introduced into the yeast Saccharomyces cerevisiae to study the fidelity of segregation. All the elements of chromosome stability have been identified from yeast, including genes, centromeres, telomeres, and origins of replication. One of the more provocative recent findings is that microtubule-based mechanochemical motors reside at the kinetochore in higher eukaryotes. Such motor proteins are likely to exhibit specific interactions with chromosomal proteins as well as spindle microtubules and provide the motive force for chromosome segregation.
A number of microtubule-based motor proteins have been isolated from the yeast. One such motor protein, dynein, is over 400,000 daltons. We have isolated the dynein gene from yeast and to our surprise, we found dynein to be dispensible for cellular growth. However, dynein-less mutants exhibit defects in spindle morphogenesis and nuclear division. We are currently examining the role of dynein and other microtubule based motors in spindle and chromosome dynamics. Our laboratory uses a combined genetic, molecular and cytological approach to gain insights into the segregation process during cell division.