Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, NIH Biomedical Research Center, Baltimore, MD, USA.
Cell Cycle. 2010 Jun 15;9(12):2317-29. doi: 10.4161/cc.9.12.11902.
Helicases catalytically unwind structured nucleic acids in a nucleoside-triphosphate-dependent and directionally specific manner, and are essential for virtually all aspects of nucleic acid metabolism. ATPase-driven helicases which translocate along nucleic acids play a role in damage recognition or unwinding of a DNA tract containing the lesion. Although classical biochemical experiments provided evidence that bulky covalent adducts inhibit DNA unwinding catalyzed by certain DNA helicases in a strand-specific manner (i.e., block to DNA unwinding restricted to adduct residence in the strand the helicase translocates), recent studies suggest more complex arrangements that may depend on the helicase under study, its assembly in a protein complex, and the type of structural DNA perturbation. Moreover, base and sugar phosphate backbone modifications exert effects on DNA helicases that suggest specialized tracking mechanisms. As a component of the replication stress response, the single-stranded DNA binding protein Replication Protein A (RPA) may serve to enable eukaryotic DNA helicases to overcome certain base lesions. Helicases play important roles in DNA damage signaling which also involve their partnership with RPA. In this review, we will discuss our current understanding of mechanistic and biological aspects of helicase action on damaged DNA.
解旋酶以核苷三磷酸依赖和方向特异性的方式催化解开结构核酸，对于核酸代谢的几乎所有方面都是必不可少的。沿核酸易位的 ATP 酶驱动的解旋酶在损伤识别或含有损伤的 DNA 链的解旋中起作用。尽管经典的生化实验提供了证据，证明大体积的共价加合物以链特异性的方式抑制某些 DNA 解旋酶催化的 DNA 解旋（即，阻止解旋仅限于解旋酶易位的链上的加合物居留），但最近的研究表明更复杂的排列方式可能取决于研究的解旋酶、其在蛋白质复合物中的组装以及结构 DNA 扰动的类型。此外，碱基和糖磷酸主链修饰对 DNA 解旋酶产生影响，表明存在专门的跟踪机制。作为复制应激反应的一部分，单链 DNA 结合蛋白复制蛋白 A (RPA) 可能有助于真核 DNA 解旋酶克服某些碱基损伤。解旋酶在 DNA 损伤信号转导中发挥重要作用，这也涉及它们与 RPA 的合作。在这篇综述中，我们将讨论我们对解旋酶在损伤 DNA 上的作用的机制和生物学方面的理解。
