Mouse Models to Understand Mutagenic Outcomes and Illegitimate Repair of DNA Damage

Abstract

Maintenance of genome integrity is critical to prevent cell death or disease. Illegitimate repair of chromosomal DNA breaks can lead to mutations and genome rearrangements which are a well-known hallmark of multiple cancers and disorders. Endogenous causes of DNA double-strand breaks (DSBs) include reactive oxygen species (ROS) and replication errors while exogenous causes of DNA breaks include ionizing radiation, UV radiation, alkylating agents, and inhibitors of topoisomerase II (Top2). Recent evidence suggests that a growing list of environmental agents or toxins and natural dietary compounds also cause DNA breaks. Understanding the consequences of exposure to a broad spectrum of DSB-inducing agents has significant implications for understanding mutagenicity, genome stability and human health. This chapter will review in vivo mouse models designed to measure DNA damage and mutagenicity, and illegitimate repair of DNA DSBs caused by exposure to environmental agents.