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Replication fork rescue in mammalian mitochondria.
Torregrosa-Muñumer, Rubén; Hangas, Anu; Goffart, Steffi; Blei, Daniel; Zsurka, Gábor; Griffith, Jack; Kunz, Wolfram S; Pohjoismäki, Jaakko L O.
Afiliación
  • Torregrosa-Muñumer R; Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101, Joensuu, Finland.
  • Hangas A; Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
  • Goffart S; Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101, Joensuu, Finland.
  • Blei D; Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, 80101, Joensuu, Finland.
  • Zsurka G; Department of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, Bonn, D-53105, Germany.
  • Griffith J; Department of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, Bonn, D-53105, Germany.
  • Kunz WS; Lineberger Comprehensive Cancer Center, University of North Carolina at, Chapel Hill, USA.
  • Pohjoismäki JLO; Department of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, Bonn, D-53105, Germany.
Sci Rep ; 9(1): 8785, 2019 06 19.
Article en En | MEDLINE | ID: mdl-31217442
Replication stalling has been associated with the formation of pathological mitochondrial DNA (mtDNA) rearrangements. Yet, almost nothing is known about the fate of stalled replication intermediates in mitochondria. We show here that replication stalling in mitochondria leads to replication fork regression and mtDNA double-strand breaks. The resulting mtDNA fragments are normally degraded by a mechanism involving the mitochondrial exonuclease MGME1, and the loss of this enzyme results in accumulation of linear and recombining mtDNA species. Additionally, replication stress promotes the initiation of alternative replication origins as an apparent means of rescue by fork convergence. Besides demonstrating an interplay between two major mechanisms rescuing stalled replication forks - mtDNA degradation and homology-dependent repair - our data provide evidence that mitochondria employ similar mechanisms to cope with replication stress as known from other genetic systems.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación del ADN / Mamíferos / Mitocondrias Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación del ADN / Mamíferos / Mitocondrias Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido