Chromatin modifications and DNA double-strand breaks: the current state of play.
The packaging and compaction of DNA into chromatin is important for all DNA-metabolism processes such as transcription, replication and repair. The involvement of chromatin modifications in transcriptional regulation is relatively well characterized, and the distinct patterns of chromatin transitions that guide the process are thought to be the result of a code on the histone proteins (histone code). In contrast to transcription, the intricate link between chromatin and responses to DNA damage has been given attention only recently. It is now emerging that specific ATP-dependent chromatin remodeling complexes (including the Ino80, Swi/Snf and RSC remodelers) and certain constitutive (methylation of lysine 79 of histone H3) and DNA damage-induced covalent histone modifications (the most well characterized being the rapid phosphorylation of histone H2A) facilitate responses to double-strand breaks. Indeed, evidence is already accumulating for a DNA repair-specific histone code. In this review, the recent advances in our understanding of the relationship between chromatin modifications and double-strand break signaling and repair is discussed.
Karagiannis
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TC
Molecular Radiation Biology, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
El-Osta
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D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D008540:Meiosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases