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Enhanced mitochondr...
Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.
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- Doimo, Mara (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Department of Women and Children Health, University of Padova, Padova, Italy
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- Chaudhari, Namrata (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Abrahamsson, Sanna (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Core Facilities, Bioinformatics,Bioinformatics and Data Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- L'Hôte, Valentin (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Nguyen, Tran V. H. (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Berner, Andreas (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Ndi, Mama (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Abrahamsson, Alva (author)
- Umeå universitet,Kemiska institutionen
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- Das, Rabindra Nath (author)
- Umeå universitet,Kemiska institutionen
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- Aasumets, Koit (author)
- Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland
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- Goffart, Steffi (author)
- Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland
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- Pohjoismäki, Jaakko L O (author)
- Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland
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- Davila Lopez, Marcela (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Core Facilities, Bioinformatics,Bioinformatics and Data Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- Chorell, Erik (author)
- Umeå universitet,Kemiska institutionen
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- Wanrooij, Sjoerd (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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(creator_code:org_t)
- Oxford University Press, 2023
- 2023
- English.
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In: Nucleic acids research. - : Oxford University Press. - 1362-4962 .- 0305-1048. ; 51:14, s. 7392-7408
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
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- Mitochondrial DNA (mtDNA) replication stalling is considered an initial step in the formation of mtDNA deletions that associate with genetic inherited disorders and aging. However, the molecular details of how stalled replication forks lead to mtDNA deletions accumulation are still unclear. Mitochondrial DNA deletion breakpoints preferentially occur at sequence motifs predicted to form G-quadruplexes (G4s), four-stranded nucleic acid structures that can fold in guanine-rich regions. Whether mtDNA G4s form in vivo and their potential implication for mtDNA instability is still under debate. In here, we developed new tools to map G4s in the mtDNA of living cells. We engineered a G4-binding protein targeted to the mitochondrial matrix of a human cell line and established the mtG4-ChIP method, enabling the determination of mtDNA G4s under different cellular conditions. Our results are indicative of transient mtDNA G4 formation in human cells. We demonstrate that mtDNA-specific replication stalling increases formation of G4s, particularly in the major arc. Moreover, elevated levels of G4 block the progression of the mtDNA replication fork and cause mtDNA loss. We conclude that stalling of the mtDNA replisome enhances mtDNA G4 occurrence, and that G4s not resolved in a timely manner can have a negative impact on mtDNA integrity.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Doimo, Mara
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Chaudhari, Namra ...
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Abrahamsson, San ...
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L'Hôte, Valentin
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Nguyen, Tran V. ...
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Berner, Andreas
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show more...
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Ndi, Mama
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Abrahamsson, Alv ...
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Das, Rabindra Na ...
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Aasumets, Koit
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Goffart, Steffi
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Pohjoismäki, Jaa ...
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Davila Lopez, Ma ...
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Chorell, Erik
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Wanrooij, Sjoerd
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Bioinformatics a ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nucleic acids re ...
- By the university
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University of Gothenburg
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Umeå University