Epigenetic therapy and DNA damage response

Chromatin regulation has been proved an essential aspect for all genomic processes, including DNA damage response (DDR). Chromatin structure can be regulated in different ways, including post-translational modifications to both the histones within the chromatin and the DNA itself. The compact nature of heterochromatin typically results in gene silencing and resistance to DNA-damaging agents, while euchromatin results in gene expression and increased sensitivity to injury. Chromatin compaction and relaxation is a dynamic process ultimately changing the gene expression profile as well as the susceptibility of cells to DNA-damaging agents. Because epigenetic modifications can be potentially reversed, the regulation of epigenetic regulators of DNA architecture may be an effective method to alter cells’ susceptibility to DNA-damaging agents used in cancer therapies. In this chapter, we discuss current and future applications of the mechanistic interplays between chromatin regulation and DNA repair for improving the efficacy and safety of cancer treatments.