Mitochondrial DNA ligase function in Saccharomyces cerevisiae

Donahue, Sarah L.; Corner, Brian E.; Bordone, Laura; Campbell, Colin

doi:10.1093/nar/29.7.1582

Cited by 29 publications

(13 citation statements)

References 33 publications

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“…None of these fusion proteins associated with the hydrogenosomes. The same is true for yeast and the pYES2/CT plasmid ( Donahue et al 2001 ; Todisco et al 2014 ). In summary, this indicates that proteins of mitochondrial ancestry have yet unspecified properties that mediate interactions with the Tom40 translocon, which was present in the earliest eukaryotes.…”

Section: Discussionmentioning

confidence: 73%

Conservation of Transit Peptide-Independent Protein Import into the Mitochondrial and Hydrogenosomal Matrix

et al. 2015

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The origin of protein import was a key step in the endosymbiotic acquisition of mitochondria. Though the main translocon of the mitochondrial outer membrane, TOM40, is ubiquitous among organelles of mitochondrial ancestry, the transit peptides, or N-terminal targeting sequences (NTSs), recognised by the TOM complex, are not. To better understand the nature of evolutionary conservation in mitochondrial protein import, we investigated the targeting behavior of Trichomonas vaginalis hydrogenosomal proteins in Saccharomyces cerevisiae and vice versa. Hydrogenosomes import yeast mitochondrial proteins even in the absence of their native NTSs, but do not import yeast cytosolic proteins. Conversely, yeast mitochondria import hydrogenosomal proteins with and without their short NTSs. Conservation of an NTS-independent mitochondrial import route from excavates to opisthokonts indicates its presence in the eukaryote common ancestor. Mitochondrial protein import is known to entail electrophoresis of positively charged NTSs across the electrochemical gradient of the inner mitochondrial membrane. Our present findings indicate that mitochondrial transit peptides, which readily arise from random sequences, were initially selected as a signal for charge-dependent protein targeting specifically to the mitochondrial matrix. Evolutionary loss of the electron transport chain in hydrogenosomes and mitosomes lifted the selective constraints that maintain positive charge in NTSs, allowing first the NTS charge, and subsequently the NTS itself, to be lost. This resulted in NTS-independent matrix targeting, which is conserved across the evolutionary divide separating trichomonads and yeast, and which we propose is the ancestral state of mitochondrial protein import.

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Section: Discussionmentioning

confidence: 73%

Conservation of Transit Peptide-Independent Protein Import into the Mitochondrial and Hydrogenosomal Matrix

et al. 2015

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“…The components of the BER machinery have also been identified in the yeast Saccharomyces cerevisiae. These include the genes for the DNA glycosylases NTG1 [You et al, 1999] and OGG1 [Singh et al, 2001], the AP endonuclease APN1 [Vongsamphanh et al, 2001], and CDC9 which encodes a DNA ligase [Donahue et al, 2001]. In yeast, the MIP1 gene encodes the replicative mtDNA Pol g and it is highly likely that this gene product also participates in BER [Foury, 1989;Stuart et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

Requirement of the Saccharomyces cerevisiae APN1 gene for the repair of mitochondrial DNA alkylation damage

Acevedo‐Torres

Fonseca-Williams

Ayala‐Torres

et al. 2009

Environ and Mol Mutagen

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The Saccharomyces cerevisiae APN1 gene that participates in base excision repair has been localized both in the nucleus and the mitochondria. APN1 deficient cells (apn1Δ) show increased mutation frequencies in mitochondrial DNA (mtDNA) suggesting that APN1 is also important for mtDNA stability. To understand APN1-dependent mtDNA repair processes we studied the formation and repair of mtDNA lesions in cells exposed to methyl methanesulfonate (MMS). We show that MMS induces mtDNA damage in a dose-dependent fashion and that deletion of the APN1 gene enhances the susceptibility of mtDNA to MMS. Repair kinetic experiments demonstrate that in wild-type cells (WT) it takes 4 hr to repair the damage induced by 0.1% MMS, whereas in the apn1Δ strain there is a lag in mtDNA repair that results in significant differences in the repair capacity between the two yeast strains. Analysis of lesions in nuclear DNA (nDNA) after treatment with 0.1% MMS shows a significant difference in the amount of nDNA lesions between WT and apn1Δ cells. Interestingly, comparisons between nDNA and mtDNA damage show that nDNA is more sensitive to the effects of MMS treatment. However, both strains are able to repair the nDNA lesions, contrary to mtDNA repair, which is compromised in the apn1Δ mutant strain. Therefore, although nDNA is more sensitive than mtDNA to the effects of MMS, deletion of APN1 has a stronger phenotype in mtDNA repair than in nDNA. These results highlight the prominent role of APN1 in the repair of environmentally induced mtDNA damage.

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“…Base excision repair is completed by the action of a DNA ligase. DNA ligase I (human: LIG1, S. cerevisiae : CDC9) is critical for the completion of nuclear BESIR; in yeast this enzyme plays a more general role, localizing to both nuclei and mitochondria ( 335 – 337 ). The activity of human LIG1 is complemented by DNA ligase III (LIG3), which localizes to both nuclei and mitochondria and specializes in SN-BESIR ( 338 ).…”

Section: Base Damage Repair Pathwaysmentioning

confidence: 99%

The current state of eukaryotic DNA base damage and repair

2015

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DNA damage is a natural hazard of life. The most common DNA lesions are base, sugar, and single-strand break damage resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. If left unrepaired, such lesions can become fixed in the genome as permanent mutations. Thus, evolution has led to the creation of several highly conserved, partially redundant pathways to repair or mitigate the effects of DNA base damage. The biochemical mechanisms of these pathways have been well characterized and the impact of this work was recently highlighted by the selection of Tomas Lindahl, Aziz Sancar and Paul Modrich as the recipients of the 2015 Nobel Prize in Chemistry for their seminal work in defining DNA repair pathways. However, how these repair pathways are regulated and interconnected is still being elucidated. This review focuses on the classical base excision repair and strand incision pathways in eukaryotes, considering both Saccharomyces cerevisiae and humans, and extends to some important questions and challenges facing the field of DNA base damage repair.

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Mitochondrial DNA ligase function in Saccharomyces cerevisiae

Cited by 29 publications

References 33 publications

Conservation of Transit Peptide-Independent Protein Import into the Mitochondrial and Hydrogenosomal Matrix

Conservation of Transit Peptide-Independent Protein Import into the Mitochondrial and Hydrogenosomal Matrix

Requirement of the Saccharomyces cerevisiae APN1 gene for the repair of mitochondrial DNA alkylation damage

The current state of eukaryotic DNA base damage and repair

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