Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties
Nei Like DNA Glycosylase 1 (NEIL1) is a DNA glycosylase, which specifically processes oxidative DNA damage by initiating base excision repair. NEIL1 recognizes and removes bases, primarily oxidized pyrimidines, which have been damaged by endogenous oxidation or exogenous mutagenic agents. NEIL1 func...
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2023
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Online Access: | https://curis.ku.dk/portal/da/publications/bowhead-neil1(717280de-ed0b-4ddd-b671-299d350c529d).html https://doi.org/10.1016/j.biochi.2022.10.014 https://curis.ku.dk/ws/files/340106279/1_s2.0_S0300908422002802_main.pdf |
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ftcopenhagenunip:oai:pure.atira.dk:publications/717280de-ed0b-4ddd-b671-299d350c529d 2024-06-09T07:45:10+00:00 Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties Holm, Signe Larsen, Rikke Møller Holst, Camilla Myrup Heide-Jørgensen, Mads Peter Steffensen, John Fleng Stevnsner, Tinna Larsen, Knud 2023 application/pdf https://curis.ku.dk/portal/da/publications/bowhead-neil1(717280de-ed0b-4ddd-b671-299d350c529d).html https://doi.org/10.1016/j.biochi.2022.10.014 https://curis.ku.dk/ws/files/340106279/1_s2.0_S0300908422002802_main.pdf eng eng info:eu-repo/semantics/openAccess Holm , S , Larsen , R M , Holst , C M , Heide-Jørgensen , M P , Steffensen , J F , Stevnsner , T & Larsen , K 2023 , ' Bowhead NEIL1 : molecular cloning, characterization, and enzymatic properties ' , Biochimie , vol. 206 , pp. 136-149 . https://doi.org/10.1016/j.biochi.2022.10.014 Aging Base excision repair Bowhead NEIL1 RNA editing article 2023 ftcopenhagenunip https://doi.org/10.1016/j.biochi.2022.10.014 2024-05-16T11:29:28Z Nei Like DNA Glycosylase 1 (NEIL1) is a DNA glycosylase, which specifically processes oxidative DNA damage by initiating base excision repair. NEIL1 recognizes and removes bases, primarily oxidized pyrimidines, which have been damaged by endogenous oxidation or exogenous mutagenic agents. NEIL1 functions through a combined glycosylase/AP (apurinic/apyrimidinic)-lyase activity, whereby it cleaves the N-glycosylic bond between the DNA backbone and the damaged base via its glycosylase activity and hydrolysis of the DNA backbone through beta-delta elimination due to its AP-lyase activity. In our study we investigated our hypothesis proposing that the cancer resistance of the bowhead whale can be associated with a better DNA repair with NEIL1 being upregulated or more active. Here, we report the molecular cloning and characterization of three transcript variants of bowhead whale NEIL1 of which two were homologous to human transcripts. In addition, a novel NEIL1 transcript variant was found. A differential expression of NEIL mRNA was detected in bowhead eye, liver, kidney, and muscle. The A-to-I editing of NEIL1 mRNA was shown to be conserved in the bowhead and two adenosines in the 242Lys codon were subjected to editing. A mass spectroscopy analysis of liver and eye tissue failed to demonstrate the existence of a NEIL1 isoform originating from RNA editing. Recombinant bowhead and human NEIL1 were expressed in E. coli and assayed for enzymatic activity. Both bowhead and human recombinant NEIL1 catalyzed, with similar efficiency, the removal of a 5-hydroxyuracil lesion in a DNA bubble structure. Hence, these results do not support our hypothesis but do not refute the hypothesis either. Nei Like DNA Glycosylase 1 (NEIL1) is a DNA glycosylase, which specifically processes oxidative DNA damage by initiating base excision repair. NEIL1 recognizes and removes bases, primarily oxidized pyrimidines, which have been damaged by endogenous oxidation or exogenous mutagenic agents. NEIL1 functions through a combined ... Article in Journal/Newspaper bowhead whale University of Copenhagen: Research Biochimie 206 136 149 |
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Open Polar |
collection |
University of Copenhagen: Research |
op_collection_id |
ftcopenhagenunip |
language |
English |
topic |
Aging Base excision repair Bowhead NEIL1 RNA editing |
spellingShingle |
Aging Base excision repair Bowhead NEIL1 RNA editing Holm, Signe Larsen, Rikke Møller Holst, Camilla Myrup Heide-Jørgensen, Mads Peter Steffensen, John Fleng Stevnsner, Tinna Larsen, Knud Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties |
topic_facet |
Aging Base excision repair Bowhead NEIL1 RNA editing |
description |
Nei Like DNA Glycosylase 1 (NEIL1) is a DNA glycosylase, which specifically processes oxidative DNA damage by initiating base excision repair. NEIL1 recognizes and removes bases, primarily oxidized pyrimidines, which have been damaged by endogenous oxidation or exogenous mutagenic agents. NEIL1 functions through a combined glycosylase/AP (apurinic/apyrimidinic)-lyase activity, whereby it cleaves the N-glycosylic bond between the DNA backbone and the damaged base via its glycosylase activity and hydrolysis of the DNA backbone through beta-delta elimination due to its AP-lyase activity. In our study we investigated our hypothesis proposing that the cancer resistance of the bowhead whale can be associated with a better DNA repair with NEIL1 being upregulated or more active. Here, we report the molecular cloning and characterization of three transcript variants of bowhead whale NEIL1 of which two were homologous to human transcripts. In addition, a novel NEIL1 transcript variant was found. A differential expression of NEIL mRNA was detected in bowhead eye, liver, kidney, and muscle. The A-to-I editing of NEIL1 mRNA was shown to be conserved in the bowhead and two adenosines in the 242Lys codon were subjected to editing. A mass spectroscopy analysis of liver and eye tissue failed to demonstrate the existence of a NEIL1 isoform originating from RNA editing. Recombinant bowhead and human NEIL1 were expressed in E. coli and assayed for enzymatic activity. Both bowhead and human recombinant NEIL1 catalyzed, with similar efficiency, the removal of a 5-hydroxyuracil lesion in a DNA bubble structure. Hence, these results do not support our hypothesis but do not refute the hypothesis either. Nei Like DNA Glycosylase 1 (NEIL1) is a DNA glycosylase, which specifically processes oxidative DNA damage by initiating base excision repair. NEIL1 recognizes and removes bases, primarily oxidized pyrimidines, which have been damaged by endogenous oxidation or exogenous mutagenic agents. NEIL1 functions through a combined ... |
format |
Article in Journal/Newspaper |
author |
Holm, Signe Larsen, Rikke Møller Holst, Camilla Myrup Heide-Jørgensen, Mads Peter Steffensen, John Fleng Stevnsner, Tinna Larsen, Knud |
author_facet |
Holm, Signe Larsen, Rikke Møller Holst, Camilla Myrup Heide-Jørgensen, Mads Peter Steffensen, John Fleng Stevnsner, Tinna Larsen, Knud |
author_sort |
Holm, Signe |
title |
Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties |
title_short |
Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties |
title_full |
Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties |
title_fullStr |
Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties |
title_full_unstemmed |
Bowhead NEIL1:molecular cloning, characterization, and enzymatic properties |
title_sort |
bowhead neil1:molecular cloning, characterization, and enzymatic properties |
publishDate |
2023 |
url |
https://curis.ku.dk/portal/da/publications/bowhead-neil1(717280de-ed0b-4ddd-b671-299d350c529d).html https://doi.org/10.1016/j.biochi.2022.10.014 https://curis.ku.dk/ws/files/340106279/1_s2.0_S0300908422002802_main.pdf |
genre |
bowhead whale |
genre_facet |
bowhead whale |
op_source |
Holm , S , Larsen , R M , Holst , C M , Heide-Jørgensen , M P , Steffensen , J F , Stevnsner , T & Larsen , K 2023 , ' Bowhead NEIL1 : molecular cloning, characterization, and enzymatic properties ' , Biochimie , vol. 206 , pp. 136-149 . https://doi.org/10.1016/j.biochi.2022.10.014 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1016/j.biochi.2022.10.014 |
container_title |
Biochimie |
container_volume |
206 |
container_start_page |
136 |
op_container_end_page |
149 |
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1801374142287577088 |