Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.822304/full |
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| author | Julia Wörtz Victoria Smith Jörg Fallmann Sabine König Sabine König Tharani Thuraisingam Paul Walther Henning Urlaub Henning Urlaub Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Thorsten Allers Frank Hille Anita Marchfelder |
| author_facet | Julia Wörtz Victoria Smith Jörg Fallmann Sabine König Sabine König Tharani Thuraisingam Paul Walther Henning Urlaub Henning Urlaub Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Thorsten Allers Frank Hille Anita Marchfelder |
| author_sort | Julia Wörtz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T00:34:51Z |
| format | Article |
| id | doaj.art-44394c7d6b2346e9bf2937e96064cb61 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-14T00:34:51Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-44394c7d6b2346e9bf2937e96064cb612022-12-22T02:22:25ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-04-011310.3389/fmicb.2022.822304822304Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA RepairJulia Wörtz0Victoria Smith1Jörg Fallmann2Sabine König3Sabine König4Tharani Thuraisingam5Paul Walther6Henning Urlaub7Henning Urlaub8Peter F. Stadler9Peter F. Stadler10Peter F. Stadler11Peter F. Stadler12Peter F. Stadler13Peter F. Stadler14Peter F. Stadler15Peter F. Stadler16Thorsten Allers17Frank Hille18Anita Marchfelder19Biology II, Ulm University, Ulm, GermanySchool of Life Sciences, University of Nottingham, Nottingham, United KingdomDepartment of Computer Science, Bioinformatics Group, Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, GermanyBioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyInstitute of Clinical Chemistry, University Medical Center Göttingen, Göttingen, GermanyCentral Facility for Electron Microscopy, Ulm University, Ulm, GermanyCentral Facility for Electron Microscopy, Ulm University, Ulm, GermanyBioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, GermanyInstitute of Clinical Chemistry, University Medical Center Göttingen, Göttingen, GermanyDepartment of Computer Science, Bioinformatics Group, Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, GermanyGerman Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, GermanyCompetence Center for Scalable Data Services and Solutions, Leipzig Research Center for Civilization Diseases, University Leipzig, Leipzig, GermanyFacultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia0Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria1Center for RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark2Santa Fe Institute, Santa Fe, NM, United States3Max Planck Institute for Mathematics in the Sciences, Leipzig, GermanySchool of Life Sciences, University of Nottingham, Nottingham, United KingdomBiology II, Ulm University, Ulm, GermanyBiology II, Ulm University, Ulm, GermanyCRISPR-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.https://www.frontiersin.org/articles/10.3389/fmicb.2022.822304/fullCRISPR-CasCas1DNA repairFen1archaeaHaloferax volcanii |
| spellingShingle | Julia Wörtz Victoria Smith Jörg Fallmann Sabine König Sabine König Tharani Thuraisingam Paul Walther Henning Urlaub Henning Urlaub Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Peter F. Stadler Thorsten Allers Frank Hille Anita Marchfelder Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair Frontiers in Microbiology CRISPR-Cas Cas1 DNA repair Fen1 archaea Haloferax volcanii |
| title | Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair |
| title_full | Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair |
| title_fullStr | Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair |
| title_full_unstemmed | Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair |
| title_short | Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair |
| title_sort | cas1 and fen1 display equivalent functions during archaeal dna repair |
| topic | CRISPR-Cas Cas1 DNA repair Fen1 archaea Haloferax volcanii |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.822304/full |
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