Biochemical, cellular and molecular identification of DNA polymerase α in yeast mitochondria

Lasserre, Jean-Paul; Plissonneau, Jacqueline; Velours, Christophe; Bonneu, Marc; Litvak, Simón; Laquel, Patricia; Castroviejo, Michel

doi:10.1016/j.biochi.2012.11.003

Cited by 5 publications

(7 citation statements)

References 65 publications

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“…Two subunits of Pol α, including the largest catalytic subunit, Pol1, and the accessory subunit Pol12, have been detected in yeast mitochondria (Lasserre et al. 2013 ). It is not known whether the mitochondrial subunits of Pol α are actually involved in the replication of mtDNA.…”

Section: Mitochondria and Genome Stabilitymentioning

confidence: 99%

See 1 more Smart Citation

Genetic instability in budding and fission yeast—sources and mechanisms

Skoneczna

Kaniak

Skoneczny

2015

FEMS Microbiology Reviews

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Cells are constantly confronted with endogenous and exogenous factors that affect their genomes. Eons of evolution have allowed the cellular mechanisms responsible for preserving the genome to adjust for achieving contradictory objectives: to maintain the genome unchanged and to acquire mutations that allow adaptation to environmental changes. One evolutionary mechanism that has been refined for survival is genetic variation. In this review, we describe the mechanisms responsible for two biological processes: genome maintenance and mutation tolerance involved in generations of genetic variations in mitotic cells of both Saccharomyces cerevisiae and Schizosaccharomyces pombe. These processes encompass mechanisms that ensure the fidelity of replication, DNA lesion sensing and DNA damage response pathways, as well as mechanisms that ensure precision in chromosome segregation during cell division. We discuss various factors that may influence genome stability, such as cellular ploidy, the phase of the cell cycle, transcriptional activity of a particular region of DNA, the proficiency of DNA quality control systems, the metabolic stage of the cell and its respiratory potential, and finally potential exposure to endogenous or environmental stress.

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Section: Mitochondria and Genome Stabilitymentioning

confidence: 99%

“…The Okazaki fragment processing apparatus comprises (1) the largest subunit of Pol α, Pol1, with its accessory subunit Pol12 (Lasserre et al. 2013 ), (2) the Pif1 helicase (Lahaye et al. 1991 ; Schulz and Zakian 1994 ) and (3) the Rad27 endonuclease (Kalifa et al.…”

Section: Mitochondria and Genome Stabilitymentioning

confidence: 99%

Genetic instability in budding and fission yeast—sources and mechanisms

Skoneczna

Kaniak

Skoneczny

2015

FEMS Microbiology Reviews

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“…DNA polymerase γ (or Pol γ) is the only DNA replicase identified in animal and fungal mitochondria. Although four other DNA polymerase activities were recently identified in Saccharomyces cerevisiae mitochondria (DNA polymerase ζ, Rev1, DNA polymerase η, and DNA polymerase α) (Zhang et al, 2006 ; Chatterjee et al, 2013 ; Lasserre et al, 2013 ), Mip1, the yeast Pol γ, is the only enzyme to be able to fully replicate mitochondrial DNA (mtDNA). Deletion of MIP1 makes the strain rho 0 , i.e., devoid of mtDNA.…”

Section: Introductionmentioning

confidence: 99%

DNA polymerase Î³ and disease: what we have learned from yeast

et al. 2015

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Mip1 is the Saccharomyces cerevisiae DNA polymerase γ (Pol γ), which is responsible for the replication of mitochondrial DNA (mtDNA). It belongs to the family A of the DNA polymerases and it is orthologs to human POLGA. In humans, mutations in POLG(1) cause many mitochondrial pathologies, such as progressive external ophthalmoplegia (PEO), Alpers' syndrome, and ataxia-neuropathy syndrome, all of which present instability of mtDNA, which results in impaired mitochondrial function in several tissues with variable degrees of severity. In this review, we summarize the genetic and biochemical knowledge published on yeast mitochondrial DNA polymerase from 1989, when the MIP1 gene was first cloned, up until now. The role of yeast is particularly emphasized in (i) validating the pathological mutations found in human POLG and modeled in MIP1, (ii) determining the molecular defects caused by these mutations and (iii) finding the correlation between mutations/polymorphisms in POLGA and mtDNA toxicity induced by specific drugs. We also describe recent findings regarding the discovery of molecules able to rescue the phenotypic defects caused by pathological mutations in Mip1, and the construction of a model system in which the human Pol γ holoenzyme is expressed in yeast and complements the loss of Mip1.

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“…Like mammalian mtDNA replication, the main replicative polymerase is a Pol γ homologue, Mip1, that consists only of the large catalytic subunit, with no PolG2 homologue identified [132,133]. In addition, Pol α has also been identified within the mitochondria in Saccharomyces cerevisiae [134]. Its dual localisation was confirmed by immunofluorescent labelling and although its function within the organelle is yet to be elucidated, it is likely to have a role in repair and gap-filling as it is unable to rescue cells lacking Mip1 [134].…”

Section: Mitochondrial Dna Replication — Copying the Circlementioning

confidence: 99%

“…In addition, Pol α has also been identified within the mitochondria in Saccharomyces cerevisiae [134]. Its dual localisation was confirmed by immunofluorescent labelling and although its function within the organelle is yet to be elucidated, it is likely to have a role in repair and gap-filling as it is unable to rescue cells lacking Mip1 [134]. In another S. cerevisiae study, Pol ζ, consisting of Rev3, Rev7 and Rev1, was also found to localise within the mitochondria and in the nucleus [135].…”

Section: Mitochondrial Dna Replication — Copying the Circlementioning

confidence: 99%

Mitochondrial DNA replication: a PrimPol perspective

Bailey

Doherty

2017

Biochemical Society Transactions

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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.

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Biochemical, cellular and molecular identification of DNA polymerase α in yeast mitochondria

Cited by 5 publications

References 65 publications

Genetic instability in budding and fission yeast—sources and mechanisms

Genetic instability in budding and fission yeast—sources and mechanisms

DNA polymerase Î³ and disease: what we have learned from yeast

Mitochondrial DNA replication: a PrimPol perspective

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