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