Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK.
Trends Biochem Sci. 2012 Feb;37(2):74-84. doi: 10.1016/j.tibs.2011.10.003. Epub 2011 Nov 24.
Structure-specific 5'-nucleases form a superfamily of evolutionarily conserved phosphodiesterases that catalyse a precise incision of a diverse range of DNA and RNA substrates in a sequence-independent manner. Superfamily members, such as flap endonucleases, exonuclease 1, DNA repair protein XPG, endonuclease GEN1 and the 5'-3'-exoribonucleases, play key roles in many cellular processes such as DNA replication and repair, recombination, transcription, RNA turnover and RNA interference. In this review, we discuss recent results that highlight the conserved architectures and active sites of the structure-specific 5'-nucleases. Despite substrate diversity, a common gating mechanism for sequence-independent substrate recognition and incision emerges, whereby double nucleotide unpairing of substrates is required to access the active site.
结构特异性 5'-核酸酶构成了一个进化上保守的磷酸二酯酶超家族,它们以序列非依赖性的方式催化广泛的 DNA 和 RNA 底物的精确切割。超家族成员,如核酸内切酶 FEN1、核酸外切酶 1、DNA 修复蛋白 XPG、内切核酸酶 GEN1 和 5'-3'-核糖核酸外切酶,在许多细胞过程中发挥关键作用,如 DNA 复制和修复、重组、转录、RNA 周转和 RNA 干扰。在这篇综述中,我们讨论了最近的结果,这些结果强调了结构特异性 5'-核酸酶的保守结构和活性位点。尽管底物多样性很大,但出现了一种用于序列非依赖性底物识别和切割的共同门控机制,其中需要双核苷酸使底物解配对才能进入活性位点。