DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair
ADP-ribosylation of proteins is crucial for fundamental cellular processes. Despite increasing examples of DNA ADP-ribosylation, the impact of this modification on DNA metabolism and cell physiology is unknown. Here, we show that the DarTG toxin-antitoxin system from enteropathogenic Escherichia col...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2020
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| _version_ | 1826291283023364096 |
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| author | Lawarée, E Jankevicius, G Cooper, C Ahel, I Uphoff, S Tang, CM |
| author_facet | Lawarée, E Jankevicius, G Cooper, C Ahel, I Uphoff, S Tang, CM |
| author_sort | Lawarée, E |
| collection | OXFORD |
| description | ADP-ribosylation of proteins is crucial for fundamental cellular processes. Despite increasing examples of DNA ADP-ribosylation, the impact of this modification on DNA metabolism and cell physiology is unknown. Here, we show that the DarTG toxin-antitoxin system from enteropathogenic Escherichia coli (EPEC) catalyzes reversible ADP-ribosylation of single-stranded DNA (ssDNA). The DarT toxin recognizes specific sequence motifs. EPEC DarG abrogates DarT toxicity by two distinct mechanisms: removal of DNA ADP-ribose (ADPr) groups and DarT sequestration. Furthermore, we investigate how cells recognize and deal with DNA ADP-ribosylation. We demonstrate that DNA ADPr stalls replication and is perceived as DNA damage. Removal of ADPr from DNA requires the sequential activity of two DNA repair pathways, with RecF-mediated homologous recombination likely to transfer ADP-ribosylation from single- to double-stranded DNA (dsDNA) and subsequent nucleotide excision repair eliminating the lesion. Our work demonstrates that these DNA repair pathways prevent the genotoxic effects of DNA ADP-ribosylation. |
| first_indexed | 2024-03-07T02:57:06Z |
| format | Journal article |
| id | oxford-uuid:afb16df2-d116-429a-9e43-b31640c9b6b1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:57:06Z |
| publishDate | 2020 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:afb16df2-d116-429a-9e43-b31640c9b6b12022-03-27T03:51:08ZDNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repairJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:afb16df2-d116-429a-9e43-b31640c9b6b1EnglishSymplectic ElementsElsevier2020Lawarée, EJankevicius, GCooper, CAhel, IUphoff, STang, CMADP-ribosylation of proteins is crucial for fundamental cellular processes. Despite increasing examples of DNA ADP-ribosylation, the impact of this modification on DNA metabolism and cell physiology is unknown. Here, we show that the DarTG toxin-antitoxin system from enteropathogenic Escherichia coli (EPEC) catalyzes reversible ADP-ribosylation of single-stranded DNA (ssDNA). The DarT toxin recognizes specific sequence motifs. EPEC DarG abrogates DarT toxicity by two distinct mechanisms: removal of DNA ADP-ribose (ADPr) groups and DarT sequestration. Furthermore, we investigate how cells recognize and deal with DNA ADP-ribosylation. We demonstrate that DNA ADPr stalls replication and is perceived as DNA damage. Removal of ADPr from DNA requires the sequential activity of two DNA repair pathways, with RecF-mediated homologous recombination likely to transfer ADP-ribosylation from single- to double-stranded DNA (dsDNA) and subsequent nucleotide excision repair eliminating the lesion. Our work demonstrates that these DNA repair pathways prevent the genotoxic effects of DNA ADP-ribosylation. |
| spellingShingle | Lawarée, E Jankevicius, G Cooper, C Ahel, I Uphoff, S Tang, CM DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair |
| title | DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair |
| title_full | DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair |
| title_fullStr | DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair |
| title_full_unstemmed | DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair |
| title_short | DNA ADP-ribosylation stalls replication and is reversed by RecF-mediated homologous recombination and nucleotide excision repair |
| title_sort | dna adp ribosylation stalls replication and is reversed by recf mediated homologous recombination and nucleotide excision repair |
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