McHugh Peter J, Sarkar Sovan
Cancer Research UK Laboratories, Weatherall Institute for Molecular Medicine, University of Oxford, Oxford, UK.
Cell Cycle. 2006 May;5(10):1044-7. doi: 10.4161/cc.5.10.2763. Epub 2006 May 15.
DNA interstrand cross-links (ICLs) present a formidable challenge to the cellular repair apparatus, but to date ICL repair pathways have proved difficult to dissect genetically. It now appears that this is partly the result of a high degree of cell cycle phase selectivity in the choice of ICL pathway employed. Here we review recent results showing that Polymerase zeta, specialized translesion plays an important role during ICL repair in G1 phase yeast cells, and that PCNA modification by ubiquitin is a key regulator of its activity. Given that this reaction can occur outside the context of S-phase, these results imply a more general role for PCNA modification in the control of DNA repair pathways through the cell cycle, which is dependent on the type of damage or repair intermediate encountered.
DNA链间交联（ICLs）对细胞修复机制构成了巨大挑战，但迄今为止，ICL修复途径在遗传学上难以剖析。现在看来，这部分是由于在选择使用的ICL途径时具有高度的细胞周期阶段选择性。在这里，我们综述了最近的研究结果，这些结果表明，聚合酶ζ这种特殊的跨损伤合成酶在G1期酵母细胞的ICL修复过程中发挥着重要作用，并且泛素对增殖细胞核抗原（PCNA）的修饰是其活性的关键调节因子。鉴于这种反应可以在S期之外发生，这些结果意味着PCNA修饰在通过细胞周期控制DNA修复途径中具有更普遍的作用，这取决于所遇到的损伤类型或修复中间体。
