The interface of transcription and DNA replication in the mitochondria - PubMed (original) (raw)

Review

The interface of transcription and DNA replication in the mitochondria

Rajesh Kasiviswanathan et al. Biochim Biophys Acta. 2012 Sep-Oct.

Abstract

DNA replication of the mitochondrial genome is unique in that replication is not primed by RNA derived from dedicated primases, but instead by extension of processed RNA transcripts laid down by the mitochondrial RNA polymerase. Thus, the RNA polymerase serves not only to generate the transcripts but also the primers needed for mitochondrial DNA replication. The interface between this transcription and DNA replication is not well understood but must be highly regulated and coordinated to carry out both mitochondrial DNA replication and transcription. This review focuses on the extension of RNA primers for DNA replication by the replication machinery and summarizes the current models of DNA replication in mitochondria as well as the proteins involved in mitochondrial DNA replication, namely, the DNA polymerase γ and its accessory subunit, the mitochondrial DNA helicase, the single-stranded DNA binding protein, topoisomerase I and IIIα and RNaseH1. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.

Published by Elsevier B.V.

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Figures

Figure 1

Figure 1. Schematic diagram of a mitochondrial DNA replication fork showing the critical proteins required for DNA replication

The nascent DNA synthesized by pol γ (green) is shown as a solid red line, while the RNA primer (jagged red line) created by the mitochondrial RNA polymerase (orange) is being degraded by RNase H1 (yellow). The mitochondrial DNA helicase (purple) unwinds the downstream DNA forming a single-stranded loop which is coated with mtSSB (light blue). Topoisomerases (brown) work to relieve torsional tension in the DNA created by unwinding.

Figure 2

Figure 2. Models of mtDNA replication

Left panel. The asymmetric or strand displacement model. Replication of the H-strand is initiated at OriH with accompanying displacement of the H-strand thus forming a D-loop. This synthesis proceeds until OriL is exposed where synthesis of the L-stand is initiated in the opposite direction. Middle panel. The strand-coupled model. Bidirectional replication is initiated from a zone near OriH followed by progression of the two forks around the mtDNA circle. Right panel. The RITOLS model. Replication of the leading strand initiates similar to the strand-displacment model but the lagging strand is initially transcribed as RNA (dashed line) before being converted to DNA.

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