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Modification of DNA by a viral enzyme and charged tRNA
Open accessPreprint — published as 10.1038/s41467-026-70671-1 · Paper page
Abstract
Bacteriophage enzymes synthesize varied and complex DNA hypermodifications. The enzyme encoded by the phage Mu gene mom is necessary for post-replicative carbamoylmethyl addition to the exocyclic amine of deoxyadenosine in DNA during the lytic phase of the viral life-cycle. The molecular details of this modification reaction, including the molecular origins of the modification itself, have long eluded understanding. Here, we demonstrate that Mom co-opts the translational machinery of the host by harvesting activated glycine from charged tRNA Gly to hypermodify adenine. Based on this insight, we report the first in vitro reconstitution of the Mu hypermodification from purified components. Using isotope labeling, we demonstrate that the carbamoyl nitrogen of the Mom modification is derived from the N 6 of adenine, indicating an on-base rearrangement of the N 6 aminoacylation product, possibly via a cyclic intermediate. Informed by the X-ray crystal structure of Mom, we have probed the location of the active site, identified a novel insertion, and established substrate specificities of the Mom enzyme.
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Metadata
- Authors
- Silva, R. M. B., Slyvka, A., Lee, Y.-J., Guan, C., Lund, S. R., Raleigh, E. A., Skowronek, K., Bochtler, M., & Weigele, P. R.
- Affiliations
- New England Biolabs (United States) (US)
- International Institute of Molecular and Cell Biology (PL)
- Corresponding author
- Bochtler, Matthias
- Weigele, Peter R.
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2023-03-25
- Volume
- 17
- Issue
- 1
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC13219725
- OpenAlex
- W7148737707
- Cited by
- 3
- References
- 1
- Citations by year
- 2025: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- New England Biolabs
- Indian Institute of Science
- Fundacja na rzecz Nauki Polskiej (POIR.04.04.00-00-5D81/17-00, START 79.2020, POIR.04.04, FNP, POIR.04.04.00-00-5D81/17-00)
- Infrastruktura PL-Grid
- Międzynarodowy Instytut Biologii Molekularnej i Komórkowej w Warszawie
- Deutsches Elektronen-Synchrotron
- Academic Computer Centre Cyfronet, AGH University of Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- N6-methyladenosine, GNAT superfamily, acetyltransferase, catalytic residues
- MeSH terms
- Adenine, Deoxyadenosines, DNA, Viral, Models, Molecular, Bacteriophage mu, RNA, Transfer, Viral Proteins
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