Wednesday, January 15, 2025
1/15/2025
While considerable attention has been given to mapping sites of solar radiation-induced mutations in a number of skin cancer-related genes, less is known about the overall distribution of the original DNA damage and how that damage influences replication and the probability of mutation fixation. The goal of this R21 project is to initially visualize and analyze the distribution of specific photoproducts (e.g. cyclobutane pyrimidine dimers (CPDs) and [6-4] pyrimidine-pyrimidone photoproducts (6-4PPs)) and relate the damage sites to selected genomic locations and areas undergoing replication. We will then determine whether genes associated with melanomagenesis, such as p16 (INK4a), p14 (ARF), BRAF, and NRAS are more susceptible to UV-induced DNA damage formation or replication stalling. These two factors increase risk for point mutations through error-prone translesion synthesis and for deletions and translocations originated during the repair of double-strand DNA breaks that are formed by the collapse of replication forks.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).