Genetic and biochemical evidence indicates that a conserved complex of five proteins, the condensin complex, is required for this process. Two proteins in this complex, Smc2p and Smc4p, are predicted to be the motor proteins that couple the chemical energy released from ATP hydrolysis to the mechanics of chromosome condensation. We are studying the yeast condensin complex, utilizing the powerful biochemistry and genetic techniques available for this organism. Our goal is to understand the mechanism by which this complex utilizes ATP to condense chromosomes. With the entire complex over-expressed and purified, we are presently using a combination of structural, kinetic, mutational and DNA topological studies to probe its mechanism.
Chromosome translocations are a form of genome instability found in many types of cancer.
Simple, non-random translocations are often causal events in the development of leukemias and lymphomas, while complex, random translocations are found in many solid tumors. Apart from translocations found in a subset of lymphoid tumors that most likely involve the RAG recombinase, very little is known about the mechanisms underlying the generation of chromosome translocations. One consistent feature of translocations is the division of genetic material originally present on one chromosome onto separate derivative chromosomes. A translocation breakpoint that falls within the human DNA will place the positive selection markers on a separate derivative chromosome from the negative selection markers. The derivative YAC is destabilized by inactivating its conditional centromere.