DNA scanning by base excision repair enzymes and implications for pathway coordination.
DNA scanning by base excision repair enzymes and implications for pathway coordination.
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DOI：
10.1016/j.dnarep.2018.08.013
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发表时间：
2018-11
期刊：
影响因子：
3.8
通讯作者：
Wilson SH
中科院分区：
文献类型：
--
作者：
Howard MJ;Wilson SH
位点特异性DNA结合蛋白必须在基因组中搜索它们的目标位点，而许多DNA修饰酶具有沿着DNA扫描寻找底物的能力。这个过程被称为渐进搜索，它通过有效地增加蛋白质的DNA结合足迹来减少搜索时间。能够进行过程搜索的蛋白质的曲目正在扩大，强调需要了解这一基本过程背后的支配原则。碱基切除DNA修复途径中的许多酶都具有过程搜索的能力。在这里，我们简要地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执行过程搜索的发现。DNA搜索的物理模型的阐明也为修复过程中的途径协调提供了一个合理的机制。当BER酶与它们的产物结合时，它能够短暂地对邻近的DNA位点进行取样，从而使下游酶能够接近，并且不需要蛋白质相互作用来进行协调。
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 proteinprotein interactions for coordination.
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