Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Curr Opin Chem Biol. 2018 Aug;45:10-17. doi: 10.1016/j.cbpa.2018.01.016. Epub 2018 Feb 13.
The introduction of site-specific DNA modifications to the genome or epigenome presents great opportunities for manipulating biological systems. Such changes are now possible through the combination of DNA-modifying enzymes with targeting modules, including dCas9, that can localize the enzymes to specific sites. In this review, we take a DNA modifying enzyme-centric view of recent advances. We highlight the variety of natural DNA-modifying enzymes-including DNA methyltransferases, oxygenases, deaminases, and glycosylases-that can be used for targeted editing and discuss how insights into the structure and function of these enzymes has further expanded editing potential by introducing enzyme variants with altered activities or by improving spatiotemporal control of modifications.
将特定于位置的 DNA 修饰引入基因组或表观基因组为操纵生物系统带来了巨大的机会。通过将 DNA 修饰酶与靶向模块（包括 dCas9）结合使用，现在可以实现这种变化，这些靶向模块可以将酶定位到特定的位点。在这篇综述中，我们从 DNA 修饰酶的角度来看待最近的进展。我们重点介绍了多种天然的 DNA 修饰酶，包括 DNA 甲基转移酶、氧化酶、脱氨酶和糖苷酶，它们可用于靶向编辑，并讨论了对这些酶的结构和功能的深入了解如何通过引入具有改变活性的酶变体或通过改善修饰的时空控制来进一步扩大编辑潜力。
