Repairing DNA damage in chromatin

摘要

Understanding how DNA repair processes occur in vivo when access to DNA is hindered by chromatin structural organisation is a current challenge. In general terms, the following sequence of events has to be considered within a chromatin environment: (ⅰ) finding a lesion (ⅱ) repairing this lesion, and (ⅲ) full restoration of a functional chromatin locus. In this review, basic principles concerning nucleosome dynamics, both intrinsic properties and those dependent on accessory factors, will be used to discuss the issue of lesion accessibility to damage-detecting proteins within chromatin. In addition, opportunities for damage detection due to chromatin alterations directly linked with transcription and replication processes will be considered. After damage detection, additional processes to enhance accessibility within chromatin may be needed to accommodate downstream repair factors or to allow DNA synthesis, resulting in interdependency between repair and accessibility mechanisms in chromatin. Finally, we will comment on the way in which chromatin assembly factors can participate in the maintenance of chromatin structures during DNA repair.