4.6 Article

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

Journal

CELLS
Volume 10, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/cells10051083

Keywords

DNA damage-induced mutagenesis; Escherichia coli SOS regulon; DNA polymerase V mutasome; β processivity clamp; TLS

Categories

Funding

  1. National Institutes of General Medical Sciences [1RM1GM130450]
  2. National Institute of Environmental Health Sciences [R35ES028343]
  3. National Institutes of Child Health and Human Development, National Institutes of Health, Intramural Research Program
  4. National Science Foundation [MCB 1817869]

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The study investigates the role of a specialized error-prone DNA polymerase in Escherichia coli and the impact of the beta-sliding processivity clamp on DNA synthesis efficiency. Results suggest that beta clamp enhances primer elongation and translesion DNA synthesis, possibly by stabilizing the polymerase and inhibiting its ATPase activity.
In the mid 1970s, Miroslav Radman and Evelyn Witkin proposed that Escherichia coli 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, umuC and umuD, along with recA. 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-2-RecA-ATP. Here, we explore the role of the beta-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 beta. The results suggest that beta 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 umuC, umuD, and recA 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.

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