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SOS 易错 DNA 聚合酶 V 突变体和β滑动夹在未受损 DNA 上协同作用,并在跨损伤合成期间发挥作用。

The SOS Error-Prone DNA Polymerase V Mutasome and β-Sliding Clamp Acting in Concert on Undamaged DNA and during Translesion Synthesis.

机构信息

Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.

Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.

出版信息

Cells. 2021 May 1;10(5):1083. doi: 10.3390/cells10051083.

Abstract

In the mid 1970s, Miroslav Radman and Evelyn Witkin proposed that must encode a specialized error-prone DNA polymerase (pol) to account for the 100-fold increase in mutations accompanying induction of the SOS regulon. By the late 1980s, genetic studies showed that SOS mutagenesis required the presence of two "UV mutagenesis" genes, and , along with . Guided by the genetics, decades of biochemical studies have defined the predicted error-prone DNA polymerase as an activated complex of these three gene products, assembled as a mutasome, pol V Mut = UmuD'C-RecA-ATP. Here, we explore the role of the β-sliding processivity clamp on the efficiency of pol V Mut-catalyzed DNA synthesis on undamaged DNA and during translesion DNA synthesis (TLS). Primer elongation efficiencies and TLS were strongly enhanced in the presence of β. The results suggest that β may have two stabilizing roles: its canonical role in tethering the pol at a primer-3'-terminus, and a possible second role in inhibiting pol V Mut's ATPase to reduce the rate of mutasome-DNA dissociation. The identification of , , and homologs in numerous strains of pathogenic bacteria and plasmids will ensure the long and productive continuation of the genetic and biochemical journey initiated by Radman and Witkin.

摘要

在 20 世纪 70 年代中期,Miroslav Radman 和 Evelyn Witkin 提出,必须编码一种专门的易错 DNA 聚合酶(pol),以解释伴随 SOS 调控子诱导而增加的 100 倍突变。到 20 世纪 80 年代末,遗传研究表明,SOS 诱变需要两个“UV 诱变”基因和的存在,以及。在遗传学的指导下,几十年来的生化研究已经将预测的易错 DNA 聚合酶定义为这三个基因产物的激活复合物,组装为 mutasome,pol V Mut = UmuD'C-RecA-ATP。在这里,我们探讨了β滑动进程性夹子在 pol V Mut 催化的未受损 DNA 上和跨损伤 DNA 合成(TLS)过程中的 DNA 合成效率中的作用。β的存在强烈增强了引物延伸效率和 TLS。结果表明,β可能有两个稳定作用:其在引物 3'-末端上系泊 pol 的典型作用,以及在抑制 pol V Mut 的 ATP 酶以降低 mutasome-DNA 解离速率方面的可能第二个作用。在许多致病性细菌和质粒菌株中发现了和的同源物,这将确保 Radman 和 Witkin 发起的遗传和生化之旅的长期和富有成效的延续。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3236/8147279/2981f999840d/cells-10-01083-g001.jpg

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