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MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage

Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and...

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Autores principales: Paulsen, Teressa, Malapati, Pumoli, Shibata, Yoshiyuki, Wilson, Briana, Eki, Rebeka, Benamar, Mouadh, Abbas, Tarek, Dutta, Anindya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599734/
https://www.ncbi.nlm.nih.gov/pubmed/34718766
http://dx.doi.org/10.1093/nar/gkab984
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author Paulsen, Teressa
Malapati, Pumoli
Shibata, Yoshiyuki
Wilson, Briana
Eki, Rebeka
Benamar, Mouadh
Abbas, Tarek
Dutta, Anindya
author_facet Paulsen, Teressa
Malapati, Pumoli
Shibata, Yoshiyuki
Wilson, Briana
Eki, Rebeka
Benamar, Mouadh
Abbas, Tarek
Dutta, Anindya
author_sort Paulsen, Teressa
collection PubMed
description Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways.
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spelling pubmed-85997342021-11-18 MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage Paulsen, Teressa Malapati, Pumoli Shibata, Yoshiyuki Wilson, Briana Eki, Rebeka Benamar, Mouadh Abbas, Tarek Dutta, Anindya Nucleic Acids Res Molecular Biology Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways. Oxford University Press 2021-10-30 /pmc/articles/PMC8599734/ /pubmed/34718766 http://dx.doi.org/10.1093/nar/gkab984 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular Biology
Paulsen, Teressa
Malapati, Pumoli
Shibata, Yoshiyuki
Wilson, Briana
Eki, Rebeka
Benamar, Mouadh
Abbas, Tarek
Dutta, Anindya
MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage
title MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage
title_full MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage
title_fullStr MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage
title_full_unstemmed MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage
title_short MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage
title_sort microdna levels are dependent on mmej, repressed by c-nhej pathway, and stimulated by dna damage
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599734/
https://www.ncbi.nlm.nih.gov/pubmed/34718766
http://dx.doi.org/10.1093/nar/gkab984
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