Abstract
PrimPol, (primase–polymerase), the most recently identified eukaryotic polymerase, has roles in both nuclear and mitochondrial DNA maintenance. PrimPol is capable of acting as a DNA polymerase, with the ability to extend primers and also bypass a variety of oxidative and photolesions. In addition, PrimPol also functions as a primase, catalysing the preferential formation of DNA primers in a zinc finger-dependent manner. Although PrimPol's catalytic activities have been uncovered in vitro, we still know little about how and why it is targeted to the mitochondrion and what its key roles are in the maintenance of this multicopy DNA molecule. Unlike nuclear DNA, the mammalian mitochondrial genome is circular and the organelle has many unique proteins essential for its maintenance, presenting a differing environment within which PrimPol must function. Here, we discuss what is currently known about the mechanisms of DNA replication in the mitochondrion, the proteins that carry out these processes and how PrimPol is likely to be involved in assisting this vital cellular process.
Highlights
Mammalian mitochondria contain multiple copies (∼1000 per cell) of a circular DNA molecule that is ∼16.5 kb in length [1]
Transcription initiated from the LSP suffers two fates: it is either terminated within a region containing three conserved sequence blocks (CSBs) and used as a primer for mitochondria DNA (mtDNA) replication, or extension continues around the mtDNA molecule to form a polycistronic transcript, which is processed further [70,71]
Mitochondrial DNA has its own specialised replicative polymerase and mechanisms that vary from those observed in the nucleus, some controversy remains within the field over the abundance and validity of the different proposed replication models
Summary
PrimPol, ( primase–polymerase), the most recently identified eukaryotic polymerase, has roles in both nuclear and mitochondrial DNA maintenance. The D-loop is thought to have many roles, including acting as a recruitment site for proteins involved in the organisation of mtDNA into nucleoid structures [16,17], maintaining dNTP pools throughout the cell cycle [18] and functioning as a key component of replication (see below). Only a few specialised proteins were thought to be required for these processes but, as techniques have improved, we are identifying numerous additional factors that play roles in the maintenance of mtDNA Many of these proteins function in both nuclear and mitochondrial compartments, such as DNA2, Fen, PIF1, Rad51C and XRCC3; some require specialised isoforms, such as Fen and PIF1, whereas others use the same isoform to perform these dual roles [20,21,22,23,24,25,26]. We review what is currently known about DNA replication processes in the mitochondrion and discuss how our newfound knowledge of PrimPol’s activities informs us about its possible roles in the duplication of mtDNA
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