Investigation of genetic networks involving genes that confer chromosome stability in S. cerevisiae and C. elegans

Chromosomes are found in all organisms that have a cell nucleus, and carry the organism’s hereditary material. During cell division, chromosomes divide and distribute equally to the daughter cells. Errors in the division process can result in daughter cells that contain an incorrect number of chromosomes. Known as aneuploidy, this state is responsible for many genetic diseases and is characterized by a specific type of genome instability known as Chromosome Instability (CIN). Because chromosome stability is a fundamental requirement across all organisms, it can be studied using simpler organisms, such as baker’s yeast. Genome wide screens on yeast have identified approximately 300 genes important for maintaining chromosome stability (CIN genes). A subset of these genes has also been found to be mutated at an elevated rate in some human cancers, which suggests that these genes contribute to tumour progression and development. Mutations in these key genome stability genes may also represent an Achilles’ heel for tumours. Enhancing chromosome instability to a point where tumour cells can no longer function and reproduce could halt their division or lead to cell death. Jessica McLellan is studying the subset of CIN genes mutated in colon cancer. She specifically aims to identify genes that, when mutated in combination with a CIN gene mutation, lead to cell death. By exploiting the mutations seen in many types of cancers, this project could lead to the development of novel cancer therapeutics that are less harmful to non-cancer cells than current treatments. McLellan’s research will increase our understanding of the complex biological processes that ensure genome stability and the mechanisms by which these processes can become deregulated.