Grant: Project Grant

Cancer develops following increased alterations within DNA, which are usually repaired by complex groups of proteins involved in DNA repair. Defects in one or more DNA repair mechanisms cause the accumulation of changes in DNA, called mutations, that increase the possibility that certain cells become tumorigenic. We work on a gene, called CUX1, that has been implicated in cancer. Normally, each gene has two copies or alleles, however, one allele of CUX1 is inactivated or lost in a fraction of human cancers. This finding suggests that the probability of developing cancer increases in cells that have only one copy of the CUX1 gene. This defines the CUX1 gene as a "tumor suppressor gene" and in our scientific jargon, we say that CUX1 is a "haploinsufficient tumor suppressor gene". The goal of our research is to understand why having only one copy of the CUX1 gene increases the probability of cancer. We already know that less of the CUX1 proteins are expressed when one copy of the gene is inactivated or lost. We want to know and demonstrate what molecular function is affected when there is a lower number of CUX1 proteins. Since the CUX1 protein plays a role in DNA repair, our hypothesis is that cells with less CUX1 are not as efficient at repairing DNA damage and therefore they accumulate changes in DNA faster than normal cells. To make a bad analogy, cancer is like winning the lottery. Cells with less CUX1 accumulate more lottery tickets than other cells and therefore they have a higher probability of getting the bad ticket.