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dc.contributor.authorOliveira, Marcos T. [UNESP]
dc.contributor.authorPontes, Carolina de Bovi
dc.contributor.authorCiesielski, Grzegorz L.
dc.date.accessioned2020-12-10T19:53:00Z
dc.date.available2020-12-10T19:53:00Z
dc.date.issued2020-01-01
dc.identifierhttp://dx.doi.org/10.1590/1678-4685-GMB-2019-0069
dc.identifier.citationGenetics And Molecular Biology. Ribeirao Pret: Soc Brasil Genetica, v. 43, n. 1, 16 p., 2020.
dc.identifier.issn1415-4757
dc.identifier.urihttp://hdl.handle.net/11449/196686
dc.description.abstractMitochondrial DNA (mtDNA) deletions are a common cause of human mitochondrial diseases. Mutations in the genes encoding components of the mitochondrial replisome, such as DNA polymerase gamma (Pol gamma) and the mtDNA helicase Twinkle, have been associated with the accumulation of such deletions and the development of pathological conditions in humans. Recently, we demonstrated that changes in the level of wild-type Twinkle promote mtDNA deletions, which implies that not only mutations in, but also dysregulation of the stoichiometry between the replisome components is potentially pathogenic. The mechanism(s) by which alterations to the replisome function generate mtDNA deletions is(are) currently under debate. It is commonly accepted that stalling of the replication fork at sites likely to form secondary structures precedes the deletion formation. The secondary structural elements can be bypassed by the replication-slippage mechanism. Otherwise, stalling of the replication fork can generate single- and double-strand breaks, which can be repaired through recombination leading to the elimination of segments between the recombination sites. Here, we discuss aberrances of the replisome in the context of the two debated outcomes, and suggest new mechanistic explanations based on replication restart and template switching that could account for all the deletion types reported for patients.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent16
dc.language.isoeng
dc.publisherSoc Brasil Genetica
dc.relation.ispartofGenetics And Molecular Biology
dc.sourceWeb of Science
dc.subjectMitochondria
dc.subjectDNA replication
dc.subjecthuman diseases
dc.subjectPol gamma
dc.subjectTwinkle
dc.titleRoles of the mitochondrial replisome in mitochondrial DNA deletion formationen
dc.typeResenha
dcterms.rightsHolderSoc Brasil Genetica
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionAuburn Univ
dc.description.affiliationUniv Estadual Paulista, Fac Ciencias Agr & Vet, Dept Tecnol, Jaboticabal, SP, Brazil
dc.description.affiliationAuburn Univ, Dept Chem, Montgomery, AL 36117 USA
dc.description.affiliationUnespUniv Estadual Paulista, Fac Ciencias Agr & Vet, Dept Tecnol, Jaboticabal, SP, Brazil
dc.identifier.doi10.1590/1678-4685-GMB-2019-0069
dc.identifier.scieloS1415-47572020000200307
dc.identifier.wosWOS:000519693500001
dc.rights.accessRightsAcesso aberto
dc.description.sponsorshipIdCNPq: 2014/02253-6
dc.description.sponsorshipIdCNPq: 2017/04372-0
dc.description.sponsorshipIdCNPq: 306974/2017-7
dc.identifier.fileS1415-47572020000200307.pdf
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