Knudsen Nina Østergaard, Andersen Sofie Dabros, Lützen Anne, Nielsen Finn Cilius, Rasmussen Lene Juel
Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark.
DNA Repair (Amst). 2009 Jun 4;8(6):682-9. doi: 10.1016/j.dnarep.2009.03.005. Epub 2009 Apr 18.
DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA, it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M.T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3-34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89-108]. Protein interactions are not only important for function, but also for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import, co-import of proteins, and alternative transport pathways. Most excision repair proteins appear to contain classical NLS sequences directing their nuclear import, however, additional import mechanisms add alternative regulatory levels to protein import, indirectly affecting protein function. Protein co-import appears to be a mechanism employed by the composite repair systems NER and MMR to enhance and regulate nuclear accumulation of repair proteins thereby ensuring faithful DNA repair.
DNA突变可通过专门的切除修复系统来规避，如碱基切除修复（BER）、核苷酸切除修复（NER）和错配修复（MMR）途径。尽管各个修复途径在抑制核DNA变化方面具有不同作用，但不同DNA修复途径的蛋白质之间显然会相互作用[Y. Wang，D. Cortez，P. Yazdi，N. Neff，S.J. Elledge，J. Qin，BASC，一种参与异常DNA结构识别和修复的BRCA1相关蛋白质的超级复合物，《基因与发育》14（2000）927 - 939；M. Christmann，M.T. Tomicic，W.P. Roos，B. Kaina，人类DNA修复机制：最新进展，《毒理学》193（2003）3 - 34；N.B. Larsen，M. Rasmussen，L.J. Rasmussen，核DNA和线粒体DNA修复：途径相似吗？《线粒体》5（2005）89 - 108]。蛋白质相互作用不仅对功能很重要，而且对修复蛋白正确定位所必需的核输入调控也很重要。本综述总结了目前关于DNA切除修复蛋白核输入机制的知识，并提供了一个模型，该模型根据不同机制对输入进行分类，包括经典核输入、蛋白质共输入和替代运输途径。大多数切除修复蛋白似乎都含有指导其核输入的经典核定位信号序列，然而，额外的输入机制为蛋白质输入增加了替代调控水平，间接影响蛋白质功能。蛋白质共输入似乎是NER和MMR复合修复系统采用的一种机制，以增强和调节修复蛋白的核积累，从而确保DNA的准确修复。
