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E. coli DNA Repair Helicase Lhr is also a Uracil-DNA Glycosylase
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  • Ed Bolt,
  • Ryan J. Buckley,
  • Karl M. Hanson,
  • Nadia R. Ahmed,
  • Christopher Cooper
Ed Bolt
University of Nottingham School of Life Sciences

Corresponding Author:[email protected]

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Ryan J. Buckley
University of Nottingham School of Life Sciences
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Karl M. Hanson
University of Huddersfield School of Applied Sciences
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Nadia R. Ahmed
University of Huddersfield School of Applied Sciences
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Christopher Cooper
University of Huddersfield School of Applied Sciences
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Abstract

DNA glycosylases protect genetic fidelity during DNA replication by removing potentially mutagenic chemically damaged DNA bases. Bacterial Lhr proteins are well-characterized DNA repair helicases that are fused to additional 600-700 amino acids of unknown function, but with structural homology to SecB chaperones and AlkZ DNA glycosylases. Here we identify that E. coli Lhr is a uracil-DNA glycosylase that depends on an active site aspartic acid residue. We show that the Lhr DNA helicase activity is functionally independent of the uracil-DNA glycosylase activity, but that the helicase domains are required for fully active uracil DNA glycosylase activity. Consistent with uracil DNA glycosylase activity, deletion of lhr from the E. coli chromosome sensitized cells to oxidative stress that triggers cytosine deamination to uracil. The ability of Lhr to translocate single-stranded DNA and remove uracil bases suggests a surveillance role to seek and remove potentially mutagenic base changes during replication stress.
16 Jan 2023Submitted to Molecular Microbiology
17 Jan 2023Submission Checks Completed
17 Jan 2023Assigned to Editor
23 Jan 2023Reviewer(s) Assigned
07 Mar 2023Editorial Decision: Revise Minor
10 Apr 20231st Revision Received
12 Apr 2023Submission Checks Completed
12 Apr 2023Assigned to Editor
15 Apr 2023Reviewer(s) Assigned
09 May 2023Review(s) Completed, Editorial Evaluation Pending
11 May 2023Editorial Decision: Revise Minor
11 Jun 20232nd Revision Received
13 Jun 2023Submission Checks Completed
13 Jun 2023Assigned to Editor
21 Jun 2023Editorial Decision: Revise Minor
24 Jun 20233rd Revision Received
26 Jun 2023Submission Checks Completed
26 Jun 2023Assigned to Editor
27 Jun 2023Editorial Decision: Accept