Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States.
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States.
DNA Repair (Amst). 2018 Nov;71:101-107. doi: 10.1016/j.dnarep.2018.08.013. Epub 2018 Aug 25.
Site-specific DNA binding proteins must search the genome to locate their target sites, and many DNA modifying enzymes have the ability to scan along DNA in search of their substrates. This process is termed processive searching, and it serves to decrease the search time by effectively increasing the DNA binding footprint of a protein. The repertoire of proteins capable of processive searching is expanding, highlighting the need to understand the governing principles behind this fundamental process. Many of the enzymes in the base excision DNA repair pathway are capable of processive searching. Here, we briefly summarize methodology for determining if a protein can scan DNA and highlight the discovery that the base excision repair DNA polymerase β performs a processive search. Elucidation of physical models for DNA searching has also provided a plausible mechanism for pathway coordination during repair. The ability of BER enzymes to transiently sample adjacent DNA sites while bound to their product confers accessibility to downstream enzymes and does not require protein-protein interactions for coordination.
特定部位的 DNA 结合蛋白必须在基因组中搜索以找到其靶标位点，许多 DNA 修饰酶具有沿着 DNA 扫描以寻找其底物的能力。该过程称为连续搜索，它通过有效增加蛋白质的 DNA 结合足迹来减少搜索时间。能够进行连续搜索的蛋白质种类在不断增加，这突出表明需要了解这一基本过程背后的控制原则。碱基切除 DNA 修复途径中的许多酶都能够进行连续搜索。在这里，我们简要总结了确定蛋白质是否可以扫描 DNA 的方法，并强调了碱基切除修复 DNA 聚合酶 β 进行连续搜索的发现。阐明 DNA 搜索的物理模型也为修复过程中途径协调提供了一个合理的机制。BER 酶在与产物结合时能够暂时对相邻的 DNA 位点进行抽样，从而使下游酶能够获得访问权限，并且不需要蛋白质-蛋白质相互作用来进行协调。
