Regulation of the Base Excision Repair Pathway by Ubiquitination

Abstract

Genome integrity is under constant threat from cellular reactive oxygen species generated by endogenous and exogenous mutagens. The base excision repair (BER) pathway consequently plays a crucial role in the repair of DNA base damage, sites of base loss and DNA single strand breaks that can cause genome instability and ultimately the development of human diseases, including premature ageing, neurodegenerative disorders and cancer. Proteins within the base excision repair pathway are increasingly being found to be regulated and controlled by post-translational modifications, and indeed ubiquitination per - forms a key role in the maintenance of repair protein levels but may also impact on protein activity and cellular localisation. This process is therefore important in maintaining an effi - cient cellular DNA damage response, and if not accurately controlled, can cause DNA damage accumulation and promote mutagenesis and genomic instability. In this chapter, we will present up-to-date information on the evidence of ubiquitination of base excision repair proteins, the enzymes involved and the molecular and cellular consequences of this process. towards these specific proteins stages