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http://hdl.handle.net/1942/34821
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DC Field | Value | Language |
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dc.contributor.author | Martins, Mariana Bonjiorno | - |
dc.contributor.author | Perez, Arina Marina | - |
dc.contributor.author | Bohr, Vilhelm A. | - |
dc.contributor.author | WILSON, David | - |
dc.contributor.author | Kobarg, Jorg | - |
dc.date.accessioned | 2021-09-08T14:50:17Z | - |
dc.date.available | 2021-09-08T14:50:17Z | - |
dc.date.issued | 2021 | - |
dc.date.submitted | 2021-09-02T10:15:24Z | - |
dc.identifier.citation | Mutagenesis, 36 (3) , p. 223 -236 | - |
dc.identifier.issn | 0267-8357 | - |
dc.identifier.uri | http://hdl.handle.net/1942/34821 | - |
dc.description.abstract | Previous studies have indicated important roles for NIMA-related kinase 1 (NEK1) in modulating DNA damage checkpoints and DNA repair capacity. To broadly assess the contributions of NEK1 to genotoxic stress and mitochondrial functions, we characterised several relevant phenotypes of NEK1 CRISPR knockout (KO) and wild-type (WT) HAP1 cells. Our studies revealed that NEK1 KO cells resulted in increased apoptosis and hypersensitivity to the alkylator methyl methanesulfonate, the radiomimetic bleomycin and UVC light, yet increased resistance to the crosslinker cisplatin. Mitochondrial functionalities were also altered in NEK1 KO cells, with phenotypes of reduced mitophagy, increased total mitochondria, elevated levels of reactive oxygen species, impaired complex I activity and higher amounts of mitochondrial DNA damage. RNA-seq transcriptome analysis coupled with quantitative real-time PCR studies comparing NEK1 KO cells with NEK1 overexpressing cells revealed that the expression of genes involved in DNA repair pathways, such as base excision repair, nucleotide excision repair and double-strand break repair, are altered in a way that might influence genotoxin resistance. Together, our studies underline and further support that NEK1 serves as a hub signalling kinase in response to DNA damage, modulating DNA repair capacity, mitochondrial activity and cell fate determination. | - |
dc.description.sponsorship | Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/02040-8, 2017/21067-7, 2017/03489-1, 2014/15982-6]; Coordenacao de Aperfeicoamento do Pessoal de Ensino Superior (CAPES) (Brasiia, DF,Brazil) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [01]; Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) (Brasiia, DF, Brazil)Conselho Nacional de Desenvolvimento Cientifico e (FAPDF) [308868/2018-8, 302534/2017-2]; Intramural Research Program of Tecnologico (CNPQ)Fundacao de Apoio a Pesquisa do Distrito Federal; the National Institute on Aging, National Institutes of Health United States Department of Health & Human Services | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.rights | © The Author(s) 2021. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. | - |
dc.title | NEK1 deficiency affects mitochondrial functions and the transcriptome of key DNA repair pathways | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 236 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 223 | - |
dc.identifier.volume | 36 | - |
local.format.pages | 14 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Kobarg, J (corresponding author), Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP, Brazil.; Kobarg, J (corresponding author), Univ Estadual Campinas, Caculdade Ciencias Farmaceut, Campinas, SP, Brazil. | - |
dc.description.notes | jorg.kobarg@fcf.unicamp.br | - |
local.publisher.place | GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1093/mutage/geab011 | - |
dc.identifier.isi | WOS:000685210200003 | - |
dc.contributor.orcid | Kobarg, Jorg/0000-0002-9419-0145 | - |
dc.identifier.eissn | 1464-3804 | - |
dc.identifier.eissn | 1464-3804 | - |
local.provider.type | wosris | - |
local.uhasselt.uhpub | yes | - |
local.description.affiliation | [Martins, Mariana Bonjiorno; Kobarg, Jorg] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP, Brazil. | - |
local.description.affiliation | [Perez, Arina Marina; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. | - |
local.description.affiliation | [Wilson, David M., III] Hasselt Univ, Biomed Res Inst, Neurosci Grp, B-3590 Diepenbeek, Belgium. | - |
local.description.affiliation | [Kobarg, Jorg] Univ Estadual Campinas, Caculdade Ciencias Farmaceut, Campinas, SP, Brazil. | - |
local.uhasselt.international | yes | - |
item.fullcitation | Martins, Mariana Bonjiorno; Perez, Arina Marina; Bohr, Vilhelm A.; WILSON, David & Kobarg, Jorg (2021) NEK1 deficiency affects mitochondrial functions and the transcriptome of key DNA repair pathways. In: Mutagenesis, 36 (3) , p. 223 -236. | - |
item.validation | ecoom 2022 | - |
item.accessRights | Open Access | - |
item.fulltext | With Fulltext | - |
item.contributor | Martins, Mariana Bonjiorno | - |
item.contributor | Perez, Arina Marina | - |
item.contributor | Bohr, Vilhelm A. | - |
item.contributor | WILSON, David | - |
item.contributor | Kobarg, Jorg | - |
crisitem.journal.issn | 0267-8357 | - |
crisitem.journal.eissn | 1464-3804 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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geab011.pdf | Published version | 2.91 MB | Adobe PDF | View/Open |
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