Chromatin modifications and radiotherapy

Radiotherapy, a widely used modality in the treatment of cancer, results in the formation of DNA double-strand breaks which result in epigenetic changes and chromatin modifications. Chromatin arch itecture is regulated by ATP-dependent chromatin remodelers, histone modifications and nucleosome reorganisation.
Together, these modifications function to alter chromatin structure in order for repair processes to occur. Histone modifications, including methylation and acctylation, are important epigenetic marks and a key modification in response to ionizing radiation is the phosphorylation of the histone variant, H2AX. Modulating DNA methylation and histone acetylation with DNA methyltrasnferase inhibitors and histone deacetylatse inhibitors is currently an active area of research for improving the therapeutic efficacy of radiation
therapy. This chapter will focus on the epigenetic events and chromatin modifications that occur following the induction of DNA double-strand breaks. Further, the effects of chromatinmodifying compounds in modulating responses to ionizing radiation are discussed.