Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron–sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron–sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron–sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.

• Publication year

  2011

• Venue

  Nucleic Acids Research

• Publication date

  2011-04-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1093/nar/gkr193PMID 21511814PMCID 3152343
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Functional

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• Mitochondria: Structure, Functions and Dysfunctions

  2011cited by this paper
• Statistical Applications in Genetics and Molecular Biology Use of Mixture Models in a Microarray-Based Screening Procedure for Detecting Differentially Represented Yeast Mutants

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• Ribosome biogenesis surveillance: probing the ribosomal protein-Mdm2-p53 pathway

  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
• Understanding the Functional Interplay between Mammalian Mitochondrial Hsp70 Chaperone Machine Components*

  2010cited by this paper
• The S-Phase Checkpoint Is Required To Respond to R-Loops Accumulated in THO Mutants

  2009cited by this paper
• Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect.

  2009cited by this paper
• Rad52.

  2009cited by this paper
• Cellular and Mitochondrial Remodeling upon Defects in Iron-Sulfur Protein Biogenesis*

  2008cited by this paper
• Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases.

  2008influential reference
• Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency.

  2008cited by this paper
• Genome instability: a mechanistic view of its causes and consequences

  2008cited by this paper
• The ISC [corrected] proteins Isa1 and Isa2 are required for the function but not for the de novo synthesis of the Fe/S clusters of biotin synthase in Saccharomyces cerevisiae.

  2007cited by this paper
• The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

  2007cited by this paper
• The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks

  2007cited by this paper
• A novel checkpoint mechanism regulating the G1/S transition.

  2007cited by this paper
• Ribosome biogenesis is sensed at the Start cell cycle checkpoint.

  2007cited by this paper
• Role of Glutaredoxin-3 and Glutaredoxin-4 in the Iron Regulation of the Aft1 Transcriptional Activator in Saccharomyces cerevisiae*

  2006cited by this paper
• affylmGUI: a graphical user interface for linear modeling of single channel microarray data

  2006cited by this paper
• The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage checkpoint.

  2006cited by this paper
• Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation.

  2005cited by this paper
• Biogenesis of cytosolic ribosomes requires the essential iron–sulphur protein Rli1p and mitochondria

  2005influential reference
• Identification of a novel member of yeast mitochondrial Hsp70‐associated motor and chaperone proteins that facilitates protein translocation across the inner membrane

  2005cited by this paper
• Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1

  2005cited by this paper
• Functional link between ribosome formation and biogenesis of iron–sulfur proteins

  2005cited by this paper
• Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis*

  2005cited by this paper
• Inactivation of the mitochondrial heat shock protein zim17 leads to aggregation of matrix hsp70s followed by pleiotropic effects on morphology and protein biogenesis.

  2005cited by this paper
• Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments

  2004cited by this paper
• Transcription of the Yeast Iron Regulon Does Not Respond Directly to Iron but Rather to Iron-Sulfur Cluster Biosynthesis*

  2004cited by this paper
• Zim17, a Novel Zinc Finger Protein Essential for Protein Import into Mitochondria*

  2004influential reference
• Npa1p is an essential trans-acting factor required for an early step in the assembly of 60S ribosomal subunits in Saccharomyces cerevisiae.

  2004cited by this paper
• The Essential ATP-binding Cassette Protein RLI1 Functions in Translation by Promoting Preinitiation Complex Assembly*♦

  2004cited by this paper
• Asymmetric Inheritance of Oxidatively Damaged Proteins During Cytokinesis

  2003cited by this paper
• Transcriptional remodeling in response to iron deprivation in Saccharomyces cerevisiae.

  2003influential reference
• Oxidative DNA damage: mechanisms, mutation, and disease

  2003cited by this paper
• A Noc Complex Specifically Involved in the Formation and Nuclear Export of Ribosomal 40 S Subunits*

  2003cited by this paper
• Aft1p and Aft2p Mediate Iron-responsive Gene Expression in Yeast through Related Promoter Elements*

  2003cited by this paper
• Yeast Rad17/Mec3/Ddc1: A sliding clamp for the DNA damage checkpoint

  2003cited by this paper
• The Putative GTPases Nog1p and Lsg1p Are Required for 60S Ribosomal Subunit Biogenesis and Are Localized to the Nucleus and Cytoplasm, Respectively

  2003cited by this paper
• Mitochondrial formation of reactive oxygen species

  2003cited by this paper
• Free radicals, antioxidants, and nutrition.

  2002cited by this paper
• Nuclear Export of 60S Ribosomal Subunits Depends on Xpo1p and Requires a Nuclear Export Sequence-Containing Factor, Nmd3p, That Associates with the Large Subunit Protein Rpl10p

  2001cited by this paper
• From the Cover: Rad52 forms DNA repair and recombination centers during S phase

  2001cited by this paper
• Mus81-Eme1 are essential components of a Holliday junction resolvase.

  2001cited by this paper
• Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae.

  2001cited by this paper
• A novel Rad24 checkpoint protein complex closely related to replication factor C.

  2000cited by this paper
• Oxidative stress promotes specific protein damage in Saccharomyces cerevisiae.

  2000cited by this paper
• Binding of double-strand breaks in DNA by human Rad52 protein

  1999cited by this paper
• Binding of double-strand breaks in DNA by human Rad52 protein

  1999cited by this paper
• The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins

  1999cited by this paper
• Mt-Hsp70 Homolog, Ssc2p, Required for Maturation of Yeast Frataxin and Mitochondrial Iron Homeostasis*

  1998influential reference
• A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation‐associated recombination

  1998cited by this paper
• RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation

  1998cited by this paper
• The Hsp70 and Hsp60 chaperone machines.

  1998cited by this paper
• Iron homeostasis, oxidative stress, and DNA damage.

  1997cited by this paper
• Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin.

  1997cited by this paper
• Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes.

  1997cited by this paper
• DNA strand annealing is promoted by the yeast Rad52 protein.

  1996cited by this paper
• Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair.

  1996cited by this paper
• Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes.

  1995cited by this paper
• Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair gene

  1995cited by this paper
• Depletion of yeast ribosomal proteins L16 or rp59 disrupts ribosome assembly

  1990cited by this paper
• Laboratory course manual for methods in yeast genetics

  1986cited by this paper
• Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae.

  1984cited by this paper
• The petite mutation in yeast. Loss of mitochondrial deoxyribonucleic acid during induction of petites with ethidium bromide.

  1970cited by this paper
• Virchows Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin

  year unknowncited by this paper

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  2022cites this paper
• Insertional mutagenesis in Chlamydomonas reinhardtii: An effective strategy for the identification of new genes involved in the DNA damage response.

  2021cites this paper
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  2021cites this paper
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  2020cites this paper
• Hsp70 Escort Protein: More Than a Regulator of Mitochondrial Hsp70

  2018cites this paper
• The elemental role of iron in DNA synthesis and repair.

  2017cites this paper
• The role of metal metabolism and heat shock protein genes on replicative lifespan of the budding yeast, Saccharomyces cerevisiae

  2016cites this paper
• Yeast Dun1 Kinase Regulates Ribonucleotide Reductase Small Subunit Localization in Response to Iron Deficiency*

  2016cites this paper
• Dun 1 regulates R 2 localization in iron deficiency 1 Yeast Dun 1 kinase regulates ribonucleotide reductase small subunit localization in response to iron deficiency

  2016cites this paper
• Mitochondria-nucleus network for genome stability.

  2015cites this paper
• The evolution and function of co-chaperones in mitochondria.

  2015cites this paper
• Impaired mitochondrial Fe-S cluster biogenesis activates the DNA damage response through different signaling mediators

  2015cites this paper
• Structural and functional studies of Hsp70-escort protein--Hep1--of Leishmania braziliensis.

  2015cites this paper
• Yeast Dun1 Kinase Regulates Ribonucleotide Reductase Inhibitor Sml1 in Response to Iron Deficiency

  2014cites this paper
• The Role Of Cardiolipin In Iron Homeostasis And Glutathione Metabolism

  2013cites this paper
• Zinc induced folding is essential for TIM15 activity as an mtHsp70 chaperone.

  2013cites this paper
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  2012cites this paper
• Biogenesis of the mitochondrial Hsp70 chaperone

  2012cites this paper
• Apn1 AP-endonuclease is essential for the repair of oxidatively damaged DNA bases in yeast frataxin-deficient cells

  2012cites this paper
• Loss of Cardiolipin Leads to Perturbation of Mitochondrial and Cellular Iron Homeostasis*

  2012cites this paper