Upon the induction of DNA damage, the
chromatin structure unwinds to allow access to
enzymes to catalyse the repair. The regulation of the winding and unwinding of
chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as
histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of
DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DNA damage. This occurs by manipulating the
chromatin structure and the expression of essential
proteins that are critical for homologous recombination and non-homologous end joining repair pathways. Inhibitors of
histone deacetylases and
DNA methyltransferases have demonstrated efficacy in the clinic and represent a promising approach for
cancer therapy. The aims of this review are to summarise the role of
histone deacetylase and
DNA methyltransferase inhibitors involved in
DNA double strand break repair and explore their current and future independent use in combination with other DNA repair inhibitors or pre-existing
therapies in the clinic.