Base Excision Repair and Nucleotide Excision Repair

Base excision repair (BER) and nucleotide excision repair (NER) are two DNA-repair pathways that, like other DNA-repair pathways except for direct reversal of DNA damage, involve sequential activities of multiple repair proteins. The two DNA-repair pathways have been studied for more than four decades, and this investigation has elucidated their crucial roles in maintaining genomic integrity particularly in response to exposure to environmental genotoxicants including ultraviolet light, cigarette smoke carcinogens, and reactive oxygen species. This chapter introduces the history and the concepts of DNA excision repair, discusses types of DNA damage processed by BER and NER, and describes the repair mechanisms. The detailed steps in these repair pathways in cells are complex and they require the coordination of the enzymatic reactions. Recent evidence indicates that DNA-damage and excision-repair proteins are key signal transducers and play critical roles for DNA-damage responses and communications between nuclei and mitochondria. Precise knowledge of BER and NER reactions should help us understand the roles that these key DNA-repair pathways play in preserving normal physiology which in turn should improve understanding of how defects in these pathways contribute to human disease with a particular emphasis on cancer.