Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand
Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiothe...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/13/3986 |
| _version_ | 1797528311480451072 |
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| author | Cécilia Hognon Antonio Monari |
| author_facet | Cécilia Hognon Antonio Monari |
| author_sort | Cécilia Hognon |
| collection | DOAJ |
| description | Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiotherapy and for immunotherapy. Despite its importance, its structure has been resolved only recently, and important questions concerning the arrangement of its active center, the interaction with the DNA substrate, and the catalytic mechanism remain unanswered. In this contribution, by performing extensive molecular dynamic simulations, both classically and at the hybrid quantum mechanics/molecular mechanics level, we evidenced the stable interaction modes of Artemis with a model DNA strand. We also analyzed the catalytic cycle providing the free energy profile and key transition states for the DNA cleavage reaction. |
| first_indexed | 2024-03-10T09:56:26Z |
| format | Article |
| id | doaj.art-188421e4f23d4e94a4905d0dabe95f72 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:56:26Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-188421e4f23d4e94a4905d0dabe95f722023-11-22T02:18:16ZengMDPI AGMolecules1420-30492021-06-012613398610.3390/molecules26133986Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double StrandCécilia Hognon0Antonio Monari1LPCT, Université de Lorraine and CNRS, UMR 7019 LPCT, F-54000 Nancy, FranceLPCT, Université de Lorraine and CNRS, UMR 7019 LPCT, F-54000 Nancy, FranceArtemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiotherapy and for immunotherapy. Despite its importance, its structure has been resolved only recently, and important questions concerning the arrangement of its active center, the interaction with the DNA substrate, and the catalytic mechanism remain unanswered. In this contribution, by performing extensive molecular dynamic simulations, both classically and at the hybrid quantum mechanics/molecular mechanics level, we evidenced the stable interaction modes of Artemis with a model DNA strand. We also analyzed the catalytic cycle providing the free energy profile and key transition states for the DNA cleavage reaction.https://www.mdpi.com/1420-3049/26/13/3986Artemis endonucleaseDNA lesion repairclassical molecular dynamicsquantum mechanics/molecular mechanicsreaction free energy profiles |
| spellingShingle | Cécilia Hognon Antonio Monari Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand Molecules Artemis endonuclease DNA lesion repair classical molecular dynamics quantum mechanics/molecular mechanics reaction free energy profiles |
| title | Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand |
| title_full | Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand |
| title_fullStr | Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand |
| title_full_unstemmed | Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand |
| title_short | Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand |
| title_sort | staring at the naked goddess unraveling the structure and reactivity of artemis endonuclease interacting with a dna double strand |
| topic | Artemis endonuclease DNA lesion repair classical molecular dynamics quantum mechanics/molecular mechanics reaction free energy profiles |
| url | https://www.mdpi.com/1420-3049/26/13/3986 |
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