Project 1: How do leading and lagging strand stress responses differ?
The replication stress response is important in responding to endogenous damage and environmental genotoxic stress to prevent developmental disorders, ageing, and cancer4. There are differences between leading and lagging strand synthesis (continuous vs discontinuous synthesis), but few studies have been performed in mammalian cells investigating the replication stress response in a strand-specific context. The goal of is to utilize multiple approaches to understand the stress response consequences of a stall or lesion in the leading or lagging strand template of DNA.
Project 2: How do lagging and leading strand mutagenesis bias differ?
Due to evidence in bacterial models systems that there are differences in strand-specific mutagenic potential we will test the mutagenic consequences of mammalian cells encountering persistent leading or lagging strand obstacles and loss of protein candidates required during leading and lagging strand stress.
Project 3: How do viruses (as genotoxins) alter human replication?
Small DNA tumor viruses likeHPV activate the human replication stress response, recruits host factors to its own genome, and induces genomic instability. The goal is to utilize multiple approaches to understand how HPV alters the human genome and replisome and what factors HPV requires from the host for its own replication. 