Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity
The DNA glycosylase NEIL2 plays a central role in maintaining genome integrity, in particular during oxidative stress, by recognizing oxidized base lesions and initiating repair of these via the base excision repair (BER) pathway. Post-translational modifications are important molecular switches tha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/2/355 |
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| author | Camilla Myrup Holst Nanna Brøndum Andersen Vibeke Thinggaard Mine Tilken Sofie Lautrup Cinzia Tesauro Tinna Stevnsner |
| author_facet | Camilla Myrup Holst Nanna Brøndum Andersen Vibeke Thinggaard Mine Tilken Sofie Lautrup Cinzia Tesauro Tinna Stevnsner |
| author_sort | Camilla Myrup Holst |
| collection | DOAJ |
| description | The DNA glycosylase NEIL2 plays a central role in maintaining genome integrity, in particular during oxidative stress, by recognizing oxidized base lesions and initiating repair of these via the base excision repair (BER) pathway. Post-translational modifications are important molecular switches that regulate and coordinate the BER pathway, and thereby enable a rapid and fine-tuned response to DNA damage. Here, we report for the first time that human NEIL2 is regulated by phosphorylation. We demonstrate that NEIL2 is phosphorylated by the two kinases cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in vitro and in human SH-SY5Y neuroblastoma cells. The phosphorylation of NEIL2 by PKC causes a substantial reduction in NEIL2 repair activity, while CDK5 does not directly alter the enzymatic activity of NEIL2 in vitro, suggesting distinct modes of regulating NEIL2 function by the two kinases. Interestingly, we show a rapid dephosphorylation of NEIL2 in response to oxidative stress in SH-SY5Y cells. This points to phosphorylation as an important modulator of NEIL2 function in this cellular model, not least during oxidative stress. |
| first_indexed | 2024-03-11T09:14:05Z |
| format | Article |
| id | doaj.art-79bd7051cfde425985f634d43819c5e5 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:05Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-79bd7051cfde425985f634d43819c5e52023-11-16T18:47:01ZengMDPI AGAntioxidants2076-39212023-02-0112235510.3390/antiox12020355Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its ActivityCamilla Myrup Holst0Nanna Brøndum Andersen1Vibeke Thinggaard2Mine Tilken3Sofie Lautrup4Cinzia Tesauro5Tinna Stevnsner6Department of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkDepartment of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkDepartment of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkDepartment of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkDepartment of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkDepartment of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkDepartment of Molecular Biology & Genetics, Aarhus University, 8000 Aarhus, DenmarkThe DNA glycosylase NEIL2 plays a central role in maintaining genome integrity, in particular during oxidative stress, by recognizing oxidized base lesions and initiating repair of these via the base excision repair (BER) pathway. Post-translational modifications are important molecular switches that regulate and coordinate the BER pathway, and thereby enable a rapid and fine-tuned response to DNA damage. Here, we report for the first time that human NEIL2 is regulated by phosphorylation. We demonstrate that NEIL2 is phosphorylated by the two kinases cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in vitro and in human SH-SY5Y neuroblastoma cells. The phosphorylation of NEIL2 by PKC causes a substantial reduction in NEIL2 repair activity, while CDK5 does not directly alter the enzymatic activity of NEIL2 in vitro, suggesting distinct modes of regulating NEIL2 function by the two kinases. Interestingly, we show a rapid dephosphorylation of NEIL2 in response to oxidative stress in SH-SY5Y cells. This points to phosphorylation as an important modulator of NEIL2 function in this cellular model, not least during oxidative stress.https://www.mdpi.com/2076-3921/12/2/355base excision repaircyclin-dependent kinase 5post-translational modificationsprotein kinase C |
| spellingShingle | Camilla Myrup Holst Nanna Brøndum Andersen Vibeke Thinggaard Mine Tilken Sofie Lautrup Cinzia Tesauro Tinna Stevnsner Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity Antioxidants base excision repair cyclin-dependent kinase 5 post-translational modifications protein kinase C |
| title | Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity |
| title_full | Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity |
| title_fullStr | Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity |
| title_full_unstemmed | Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity |
| title_short | Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity |
| title_sort | phosphorylation of the human dna glycosylase neil2 is affected by oxidative stress and modulates its activity |
| topic | base excision repair cyclin-dependent kinase 5 post-translational modifications protein kinase C |
| url | https://www.mdpi.com/2076-3921/12/2/355 |
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