捉迷藏：DNA糖基化酶如何在大量未受损碱基中找到氧化损伤的DNA碱基？
Hide and seek: How do DNA glycosylases locate oxidatively damaged DNA bases amidst a sea of undamaged bases?
作者信息
Lee Andrea J, Wallace Susan S
机构信息
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, 95 Carrigan Drive, Burlington, VT 05405, USA.
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, 95 Carrigan Drive, Burlington, VT 05405, USA.
出版信息
Free Radic Biol Med. 2017 Jun;107:170-178. doi: 10.1016/j.freeradbiomed.2016.11.024. Epub 2016 Nov 16.
The first step of the base excision repair (BER) pathway responsible for removing oxidative DNA damage utilizes DNA glycosylases to find and remove the damaged DNA base. How glycosylases find the damaged base amidst a sea of undamaged bases has long been a question in the BER field. Single molecule total internal reflection fluorescence microscopy (SM TIRFM) experiments have allowed for an exciting look into this search mechanism and have found that DNA glycosylases scan along the DNA backbone in a bidirectional and random fashion. By comparing the search behavior of bacterial glycosylases from different structural families and with varying substrate specificities, it was found that glycosylases search for damage by periodically inserting a wedge residue into the DNA stack as they redundantly search tracks of DNA that are 450-600bp in length. These studies open up a wealth of possibilities for further study in real time of the interactions of DNA glycosylases and other BER enzymes with various DNA substrates.
碱基切除修复（BER）途径负责去除氧化性DNA损伤，其第一步利用DNA糖基化酶来寻找并去除受损的DNA碱基。长期以来，在碱基切除修复领域，糖基化酶如何在大量未受损碱基中找到受损碱基一直是个问题。单分子全内反射荧光显微镜（SM TIRFM）实验让人们得以令人兴奋地深入了解这种搜索机制，并发现DNA糖基化酶以双向随机方式沿着DNA主链进行扫描。通过比较来自不同结构家族且具有不同底物特异性的细菌糖基化酶的搜索行为，发现糖基化酶在冗余搜索长度为450 - 600bp的DNA序列时，会周期性地将一个楔形残基插入DNA堆积中以寻找损伤。这些研究为进一步实时研究DNA糖基化酶和其他碱基切除修复酶与各种DNA底物之间的相互作用开辟了大量可能性。
Zotero 插件