Cross-species characterization of proteins involved in genomic stability

Cell division is required for the development, growth, renewal and repair of all organisms, including humans. During cell division, the cell’s genomic information – stored in the chromosomes – is replicated (copied) so that each of the resulting daughter cells receives a complete set of genetic material. Proper segregation of chromosomes to daughter cells during cell division is critical to their continued survival, and chromosome missegregation has been observed in a majority of cancers. However, the connection between the increased rate of chromosome missegregation observed in cancer, and the development of the cancer itself, remains unclear. Because chromosome segregation is a fundamental mechanism in all organisms, baker’s yeast can be used as a model to study this process. Many yeast genes and proteins involved in chromosome segregation appear to be conserved across evolution between yeast and humans. One such protein in yeast is Ctf4, which has a human counterpart called Wdhd1. Ctf4 plays a critical role in ensuring faithful chromosome segregation during cell division, though its biochemical function is not fully understood. The yeast CTF4 gene also appears to interact genetically with a number of yeast genes whose human counterparts are known to be mutated in cancer. Derek van Pel is further characterizing both the human and yeast proteins' roles in this chromosome segregation. He is using biochemical techniques to isolate any other proteins within the cell with which these proteins interact. Such interactions will then offer clues to the function of these proteins. Derek’s research will shed light on the role of Ctf4/Wdhd1 in ensuring proper chromosome segregation, and possibly the role of this process in cancer development. Understanding these genetic interactions may also lead directly to new therapeutic avenues for cancer.