Uncovering How RAD51 Paralog Mutations Contribute to Cancer Predisposition
Uncovering How Rad51 Paralog Mutations Contribute to Cancer Predisposition
Kara A. Bernstein, PhD
Assistant Professor, Department of Microbiology and Molecular Genetics
University of Pittsburgh
Changes in DNA, known as mutations, can arise during cancer and in some cases can also be a cause of cancer. Every day, our DNA is damaged from internal sources, such as free radicals, as well as external sources, such as ultraviolet light or radiation. Damaged DNA can lead to mutations and, in healthy cells, many proteins work together to repair DNA damage as it arises. One of the most toxic types of DNA damage a cell can encounter is called a DNA double-strand break (DSB) – even one unrepaired double-strand break will result in cell death. Cells have specialized proteins that work to fix DSBs. The repair process can stop working, however, if the DNA repair proteins are themselves mutated. Mutations in DNA repair pathways have been linked to a number of human cancers. This study focuses on a group of DSB repair proteins, known as the RAD51 paralogs, which have been linked to cancer susceptibility, particularly in breast and ovarian cancers. There are five RAD51 paralogs that work together to repair broken DNA and maintain the health of a cell. The goals of this project are to 1) understand the importance of the RAD51 paralogs in repairing DSBs; 2) understand why people who have mutations in any one of the RAD51 paralogs are more likely to develop cancer; and 3) determine novel methods for treating RAD51 paralog mutant cancers. The ultimate goal is to uncover individualized cancer treatments for these particular tumors to ensure that these patients will have the best outcomes.
Updated: May 2016