The Mitochondrial DNA Helicase TWINKLE Can Assemble on a Closed Circular Template and Support Initiation of DNA Synthesis

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2011 Aug 16

PMID 21840902

Citations 28

Authors

Elisabeth Jemt

Geraldine Farge

Stefan Backstrom

Teresa Holmlund

Claes M Gustafsson

Maria Falkenberg

Affiliations

Soon will be listed here.

Abstract

Mitochondrial DNA replication is performed by a simple machinery, containing the TWINKLE DNA helicase, a single-stranded DNA-binding protein, and the mitochondrial DNA polymerase γ. In addition, mitochondrial RNA polymerase is required for primer formation at the origins of DNA replication. TWINKLE adopts a hexameric ring-shaped structure that must load on the closed circular mtDNA genome. In other systems, a specialized helicase loader often facilitates helicase loading. We here demonstrate that TWINKLE can function without a specialized loader. We also show that the mitochondrial replication machinery can assemble on a closed circular DNA template and efficiently elongate a DNA primer in a manner that closely resembles initiation of mtDNA synthesis in vivo.

Citing Articles

In Vitro Assays of TWINKLE Function.

Uhler J, Alexandersson U, Falkenberg M Methods Mol Biol. 2023; 2615:191-201.

PMID: 36807793 DOI: 10.1007/978-1-0716-2922-2_14.

The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ.

Johnson L, Singh A, Patel S J Biol Chem. 2022; 299(1):102797.

PMID: 36528058 PMC: 9860392. DOI: 10.1016/j.jbc.2022.102797.

Structural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase.

Li Z, Kaur P, Lo C, Chopra N, Smith J, Wang H Nucleic Acids Res. 2022; 50(20):11965-11978.

PMID: 36400570 PMC: 9723800. DOI: 10.1093/nar/gkac1089.

Mitochondrial DNA maintenance in Drosophila melanogaster.

Rodrigues A, Novaes A, Ciesielski G, Oliveira M Biosci Rep. 2022; 42(11).

PMID: 36254835 PMC: 9653094. DOI: 10.1042/BSR20211693.

Method for the structural analysis of Twinkle mitochondrial DNA helicase by cryo-EM.

Riccio A, Bouvette J, Longley M, Krahn J, Borgnia M, Copeland W Methods. 2022; 205:263-270.

PMID: 35779765 PMC: 9398961. DOI: 10.1016/j.ymeth.2022.06.012.

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