Caenorhabditis elegans par2.1/mtssb-1 is essential for mitochondrial DNA replication and its defect causes comprehensive transcriptional alterations including a hypoxia response

Sugimoto, Tomoko; Mori, Chihiro; Takanami, Takako; Sasagawa, Yohei; Saito, Rumiko; Ichiishi, Eiichiro; Higashitani, Akihiro

doi:10.1016/j.yexcr.2007.08.015

Cited by 29 publications

(37 citation statements)

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“…mtSSB is a single-stranded DNA binding protein with properties similar to E. coli SSB (12,30). mtSSB is a key component of the mitochondrial DNA replication machinery and is an essential gene in several organisms for which this question has been examined (36,46). Like E. coli SSB, mtSSB stabilizes single-strand formation and stimulates homologous strand exchange by RecA (15).…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication

Wiedmer

Wang

Zhou

et al. 2008

J Virol

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Disruption of cellular metabolic processes and usurpation of host proteins are hallmarks of herpesvirus lytic infection. Epstein-Barr virus (EBV) lytic replication is initiated by the immediate-early protein Zta. Zta is a multifunctional DNA binding protein that stimulates viral gene transcription, nucleates a replication complex at the viral origin of lytic replication, and inhibits cell cycle proliferation. To better understand these functions and identify cellular collaborators of Zta, we purified an epitope-tagged version of Zta in cells capable of supporting lytic replication. FLAG-tagged Zta was purified from a nuclear fraction using FLAG antibody immunopurification and peptide elution. Zta-associated proteins were isolated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and identified by mass spectrometry. The Zta-associated proteins included members of the HSP70 family and various single-stranded DNA and RNA binding proteins. The nuclear replication protein A subunits (RPA70 and RPA32) and the human mitochondrial single-stranded DNA binding protein (mtSSB) were confirmed by Western blotting to be specifically enriched in the FLAG-Zta immunopurified complex. mtSSB coimmunoprecipitated with endogenous Zta during reactivation of EBVpositive Burkitt lymphoma and lymphoblastoid cell lines. Small interfering RNA depletion of mtSSB reduced Zta-induced lytic replication of EBV but had only a modest effect on transcription activation function. A point mutation in the Zta DNA binding domain (C189S), which is known to reduce lytic cycle replication, eliminated mtSSB association with Zta. The predominantly mitochondrial localization of mtSSB was shifted to partly nuclear localization in cells expressing Zta. Mitochondrial DNA synthesis and genome copy number were reduced by Zta-induced EBV lytic replication. We conclude that Zta interaction with mtSSB serves the dual function of facilitating viral and blocking mitochondrial DNA replication.

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Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication

Wiedmer

Wang

Zhou

et al. 2008

J Virol

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“…To investigate whether C. elegans checkpoint controlrelated genes participate in mtDNA maintenance, we compared mtDNA copy numbers in wild-type, atl-1(tm853, ATR homolog), atm-1(gk186, ATM homolog), and cep-1(w40, p53 homolog) adult hermaphrodites [3 days old from the laid egg (3d): young adult stage] using real-time PCR and normalizing against chrDNA copy number (Sugimoto et al 2008). atl-1(tm853) and atm-1(gk186) delete a 720-bp region within the exon-7 and a 548-bp region within the parts of intron 1 and exon 2, respectively (http://www.wormbase.org).…”

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confidence: 99%

Maintenance of Mitochondrial DNA by the Caenorhabditis elegans ATR Checkpoint Protein ATL-1

2008

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Here we show that inactivation of the ATR-related kinase ATL-1 results in a significant reduction in mitochondrial DNA (mtDNA) copy numbers in Caenorhabditis elegans. Although ribonucleotide reductase (RNR) expression and the ATP/dATP ratio remained unaltered in atl-1 deletion mutants, inhibition of RNR by RNAi or hydroxyurea treatment caused further reductions in mtDNA copy number. These results suggest that ATL-1 functions to maintain mtDNA independently of RNR. P ROTEIN kinases in the ataxia-telangiectasia mutated (ATM) family initiate a well-characterized response to DNA damage, resulting in cell-cycle arrest, DNA repair, or apoptosis (Abraham 2001;Shiloh 2003). This family is highly conserved among eukaryotes, comprising two related proteins: ATM and ATR (AT mutant and rad3 1 related) in humans; Tel1 and Mec1/Esr1 in Saccharomyces cerevisiae; Tel1 and Rad3 in Schizosaccharomyces pombe; and ATM-1 and ATL-1 in

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“…Mitochondria functions in oxidative phosphorylation, heme, lipid, amino acid biosynthesis, and fatty acid oxidation among other functions (Sugimoto, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria contain their own genome, mtDNA, which consists of a 16.5-kb circular double-stranded DNA (dsDNA) molecule containing 37 genes . Mitochondria functions in oxidative phosphorylation, heme, lipid, amino acid biosynthesis, and fatty acid oxidation among other functions (Sugimoto, 2008). The major source of ATP in cortical neurons is provided by mitochondrial oxidative phosphorylation Waldbaum and Patel, 2010a).…”

Section: Discussionmentioning

confidence: 99%

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Prenatal Environmental Exposure and Neurodevelopmentally Important Gene Expression in Malformed Brain Tissue from Pediatric Intractable Epilepsy Patients

Luna¹

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Caenorhabditis elegans par2.1/mtssb-1 is essential for mitochondrial DNA replication and its defect causes comprehensive transcriptional alterations including a hypoxia response

Cited by 29 publications

References 54 publications

Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication

Epstein-Barr Virus Immediate-Early Protein Zta Co-Opts Mitochondrial Single-Stranded DNA Binding Protein To Promote Viral and Inhibit Mitochondrial DNA Replication

Maintenance of Mitochondrial DNA by the Caenorhabditis elegans ATR Checkpoint Protein ATL-1

Prenatal Environmental Exposure and Neurodevelopmentally Important Gene Expression in Malformed Brain Tissue from Pediatric Intractable Epilepsy Patients

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