Gontijo Alisson M de M C, Green Catherine M, Almouzni Geneviève
UMR 218 Institute Curie, Recherche, 26 rue d'Ulm, 75248 Paris 5, France.
Biochimie. 2003 Nov;85(11):1133-47. doi: 10.1016/j.biochi.2003.10.018.
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.
了解当DNA的获取因染色质结构组织而受阻时,DNA修复过程如何在体内发生,是当前面临的一项挑战。一般而言,在染色质环境中必须考虑以下一系列事件:(i)发现损伤;(ii)修复该损伤;以及(iii)功能性染色质位点的完全恢复。在本综述中,将运用有关核小体动力学的基本原理,包括其内在特性以及那些依赖辅助因子的特性,来讨论染色质内损伤检测蛋白对损伤的可及性问题。此外,还将考虑由于与转录和复制过程直接相关的染色质改变而进行损伤检测的机会。在损伤检测之后,可能需要其他过程来增强染色质内的可及性,以容纳下游修复因子或允许DNA合成,从而导致染色质中修复与可及性机制之间的相互依存关系。最后,我们将评论染色质组装因子在DNA修复过程中参与维持染色质结构的方式。