Chromatin remodeling finds its place in the DNA double-strand break response.
The accurate repair of chromosomal double-strand breaks (DSBs) arising from exposure to exogenous agents, such as ionizing radiation (IR) and radiomimetic drugs is crucial in maintaining genomic integrity, cellular viability and the prevention of tumorigenesis. Eukaryotic cells have evolved efficient mechanisms that sense and respond to DSBs. The DNA DSB response is facilitated by hierarchical signaling networks that orchestrate chromatin structural changes, cell-cycle checkpoints and multiple enzymatic activities to repair the broken DNA ends. Sensors and transducers signal to numerous downstream cellular effectors which function primarily by substrate posttranslational modifications including phosphorylation, acetylation, methylation and ubiquitylation. In particular, the past several years have provided important insight into the role of chromatin remodeling and histones-specific modifications to control DNA damage detection, signaling and repair. This review summarizes recently identified factors that influence this complex process and the repair of DNA DSBs in eukaryotic cells.
Pandita
Tej K
TK
Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63108, USA. pandita@wustl.edu
Richardson
Christine
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D011494:Protein Kinases