Topic Overview:

Oxidative DNA damage is frequently caused by environmental agents (e.g., chemical toxicants, solar light, and ionizing radiation) and endogenously by normal cellular metabolism. Defective cellular responses to oxidative DNA damage may give rise to genomic instability, disrupted epigenetic inheritance, and tumorigenesis. To understand the complex cellular processes that are engaged in the repair of oxidative DNA damage, Lan and her colleagues have developed several new and powerful approaches to analyze the damage and its repair at specific genome loci. These in situ strategies allow the precise delineation of site-specific molecular mechanisms and the identification of novel components of oxidative DNA damage repair that may be unique to those sites—for example, heterochromatic versus euchromatic DNA or telomeric versus whole genomic DNA. Lan and her colleagues have also been focusing on understanding how chromatin remodeling, epigenetic modification, and transcription affect oxidative DNA damage responses. In her lecture, Lan will discuss the mechanisms by which nucleosomal structure aids efficient DNA damage removal and the connection between chromatin dynamics and DNA damage repair and how this relation affects cancer, aging, and neurodevelopmental defects.