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  Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair

Wortz, J., Smith, V., Fallmann, J., König, S., Thuraisingam, T., Walther, P., et al. (2022). Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair. Frontiers in Microbiology, 13: 822304. doi:10.3389/fmicb.2022.822304.

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 Creators:
Wortz, Julia, Author
Smith, Victoria, Author
Fallmann, Joerg, Author
König, Sabine1, Author           
Thuraisingam, Tharani, Author
Walther, Paul, Author
Urlaub, Henning1, Author           
Stadler, Peter F., Author
Allers, Thorsten, Author
Hille, Frank, Author           
Marchfelder, Anita, Author
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              

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Free keywords: CRISPR-Cas, Cas1, DNA repair, Fen1, archaea, Haloferax volcanii
 Abstract: CRISPR-Cas constitutes an adaptive prokaryotic defence system against invasive nucleic acids like viruses and plasmids. Beyond their role in immunity, CRISPR-Cas systems have been shown to closely interact with components of cellular DNA repair pathways, either by regulating their expression or via direct protein-protein contact and enzymatic activity. The integrase Cas1 is usually involved in the adaptation phase of CRISPR-Cas immunity but an additional role in cellular DNA repair pathways has been proposed previously. Here, we analysed the capacity of an archaeal Cas1 from Haloferax volcanii to act upon DNA damage induced by oxidative stress and found that a deletion of the cas1 gene led to reduced survival rates following stress induction. In addition, our results indicate that Cas1 is directly involved in DNA repair as the enzymatically active site of the protein is crucial for growth under oxidative conditions. Based on biochemical assays, we propose a mechanism by which Cas1 plays a similar function to DNA repair protein Fen1 by cleaving branched intermediate structures. The present study broadens our understanding of the functional link between CRISPR-Cas immunity and DNA repair by demonstrating that Cas1 and Fen1 display equivalent roles during archaeal DNA damage repair.

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Language(s): eng - English
 Dates: 2022-04-15
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.3389/fmicb.2022.822304
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Project name : Work in the AM laboratory as well as in the HU laboratory was funded by the DFG priority programme “CRISPR-Cas functions beyond defence” SPP2141 (Ma1538/25-1 and UR225- 7/1). Data analysis was in part funded by the German Federal Ministry for Education and Research [BMBF 031A538B (de.NBI/RBC)] to PS. This work was also supported by the Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M008770/1] to VS. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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Title: Frontiers in Microbiology
  Abbreviation : Front. Microbiol.
Source Genre: Journal
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Publ. Info: Lausanne : Frontiers Media
Pages: - Volume / Issue: 13 Sequence Number: 822304 Start / End Page: - Identifier: ISSN: 1664-302X
CoNE: https://pure.mpg.de/cone/journals/resource/1664-302X