Core D: DNA Damage Signaling and Repair

SUMMARY - DNA DAMAGE SIGNALING AND REPAIR CORE D Revelo & Schmidt The DNA Damage Signaling and Repair Core D, part of the proposed Minnesota Nathan Shock Center on Genome Instability and Aging, will provide innovative approaches and reagents for the assessment of proteins crucial to DNA damage, the DNA damage response (DDR) and senenescence in aging as well as quantitation of DNA repair activity. Leveraging cutting-edge techniques like cytometry by time of flight (CyTOF) and a functional nucleotide excision repair (NER) assay, we will assist researchers in studying aging-related DNA damage dynamics. These approaches have been validated in our Core and are unique strengths of the Institute on the Biology of Aging and Metabolism at the University of Minnesota. The Core will help researchers use CyTOF and NER approaches to investigate DNA damage, DDR, senescence, and DNA repair activity during aging. Our focus on these approaches makes our Core unique as CyTOF and NER approaches are not available at any other Nathan Shock Center. The Specific Aims of Core D are to provide a quality-controlled platform and custom reagents for the assessment of DNA damage and repair-associated proteins by CyTOF (Aim 1) and provide a platform to functionally assess NER capacity for aging studies (Aim 2). This Core will provide consistent and validated state-of-the-art approaches to investigate DNA damage and repair that are unique among all Nathan Shock Centers. Our assays will build the foundation on which additional functional DNA repair assays (e.g., base excision repair, DNA double-strand break repair, DNA inter-strand crosslink repair) can be used in aging studies. As the study of DNA damage and how damage may be restored has clinical implications in aging research, our Core will provide robust approaches for their assessment.