Novel DNA Mismatch Repair Interacting Proteins in Colon and Endometrial Cancers

The environment in which we carry out our daily lives is full of things that can cause damage to DNA, the blueprint for all cellular functions. These damaged templates then make faulty cellular components and can cause cancer. Luckily, we have a number of repair systems to protect our DNA from the every day wear and tear caused by cell function and from environmental damage (such as UV exposure and pollution). My laboratory studies one of these repair systems called DNA mismatch repair. When a person loses the function of DNA mismatch repair their cells accumulate a high number of DNA mutations and tissues that continually renew, like stomach and colon lining and uterine tissue are at risk for developing tumors. Cells that have lost mismatch repair also don’t respond to very common types of chemotherapy. Therefore, understanding how this pathway works is very important for understanding cancer development, genetic screening and for decisions about treatment. This pathway is so important to survival that it has not changed much between ourselves and the budding yeast species known as Baker’s Yeast. My lab uses this budding yeast system to carry out studies of how the pathway works that would either be impossible or extremely time consuming and expensive to do in human cells or mice. We then are able to use that knowledge to design targeted studies for our human cancer cells in the lab. My lab is currently very interested in how loss of the DNA mismatch repair pathway leads to chemotherapy resistance. An important part of understanding the pathway is understanding how and where the different protein components of the pathway physically interact. While studying this as a Postdoctoral Fellow I discovered a new type of interaction site with a key mismatch repair protein that is needed to recognize damage. This led to the discovery of new protein players that weren’t known to previously be involved in the pathway. We are studying how these new genes change cancer development and sensitivity to chemotherapy using both our yeast system and human tumor cells. Understanding the role these physical interactions play tumor development and in chemotherapy response will hopefully allow for better choices to be made on treatment options for individual patients and for design of targeted therapy for patients who don’t receive benefit from current treatment with chemotherapeutic agents.