Coordination of epigenetic events.
During the course of DNA damage a complex repertoire of molecular signals, chromatin determinants and specific transcription factors are set in motion for repair. In many instances, the response pathway can be characterized by profound changes in molecular remodeling and is intimately linked with DNA replication and gene transcription. Our understanding of the molecular pathways has come from scientific developments that represent many disparate disciplines, such as cancer (epi)genetics, chromatin modifications during cellular development and the emerging prominence of epigenetic events in human disease. These multidisciplinary areas reveal a functional relationship and suggest that repair and transcription must coincide in the context of chromatin. We have come to appreciate the repair process and the role of transcriptional components in a sophisticated program of epigenetic regulation, and we have learnt much since the first description of the nucleosome as a spheroid disklike unit. The coordinated and ordered response to DNA damage can specify structures that mobilize and remodel nucleosomes. Investigators will undoubtedly continue to explore the structural and functional states of DNA damage repair and continue to profile the sequence of events and scrutinize the molecular signatures that specify these changes in chromatin dynamics, genomic stability and transcriptional performance. In this special issue, authors have contributed reviews that discuss hypotheses and results regarding DNA damage repair and transcription. The topics covered range from DNA repair in a chromatin environment to the deadly double-strand break, histone modifications to ATP-dependent chromatin remodeling, gene silencing in cancer to apoptosis and regulation of chromatin dynamics by DNA methylation. The scene is set for a new view of damage detection and repair by the coordination of epigenetic states.
El-Osta
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Baker Medical Research Institute, Epigenetics in Human Health and Disease Laboratory, The Alfred Medical Research and Education Precinct (AMREP), Prahran, Victoria, Australia. assam.el-osta@baker.edu.au
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D014158:Transcription, Genetic