Advances in understanding the coupling of DNA base modifying enzymes to processes involving base excision repair.

This chapter describes some of the recent, exciting developments that have characterized and connected processes that modify DNA bases with DNA repair pathways. It begins with AID/APOBEC or TET family members that covalently modify bases within DNA. The modified bases, such as uracil or 5-formylcytosine, are then excised by DNA glycosylases including UNG or TDG to initiate base excision repair (BER). BER is known to preserve genome integrity by removing damaged bases. The newer studies underscore the necessity of BER following enzymes that deliberately damage DNA. This includes the role of BER in antibody diversification and more recently, its requirement for demethylation of 5-methylcytosine in mammalian cells. The recent advances have shed light on mechanisms of DNA demethylation, and have raised many more questions. The potential hazards of these processes have also been revealed. Dysregulation of the activity of base modifying enzymes, and resolution by unfaithful or corrupt means can be a driver of genome instability and tumorigenesis. The understanding of both DNA and histone methylation and demethylation is now revealing the true extent to which epigenetics influence normal development and cancer, an abnormal development.