The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ.

Catalytic Domain DNA Polymerase III / metabolism DNA Repair DNA Replication DNA-Directed DNA Polymerase / metabolism Iron-Sulfur Proteins / metabolism Protein Binding Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / metabolism Transcription Factors / metabolism

Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
04 06 2021
Historique:
accepted: 16 05 2021
revised: 22 04 2021
received: 09 03 2021
pubmed: 22 5 2021
medline: 7 7 2021
entrez: 21 5 2021
Statut: ppublish

Résumé

Iron-sulfur clusters (4Fe-4S) exist in many enzymes concerned with DNA replication and repair. The contribution of these clusters to enzymatic activity is not fully understood. We identified the MET18 (MMS19) gene of Saccharomyces cerevisiae as a strong mutator on GC-rich genes. Met18p is required for the efficient insertion of iron-sulfur clusters into various proteins. met18 mutants have an elevated rate of deletions between short flanking repeats, consistent with increased DNA polymerase slippage. This phenotype is very similar to that observed in mutants of POL3 (encoding the catalytic subunit of Pol δ) that weaken binding of the iron-sulfur cluster. Comparable mutants of POL2 (Pol ϵ) do not elevate deletions. Further support for the conclusion that met18 strains result in impaired DNA synthesis by Pol δ are the observations that Pol δ isolated from met18 strains has less bound iron and is less processive in vitro than the wild-type holoenzyme.

Identifiants

DOI: 10.1093/nar/gkab371 PMID: 34019669 PMC: PMC8191807
pubmed: 34019669
pii: 6279846
doi: 10.1093/nar/gkab371
pmc: PMC8191807
doi:

Substances chimiques

Iron-Sulfur Proteins 0
MET18 protein, S cerevisiae 0
POL3 protein, S cerevisiae 0
Pol32 protein, S cerevisiae 0
Saccharomyces cerevisiae Proteins 0
Transcription Factors 0
DNA Polymerase III EC 2.7.7.7
DNA-Directed DNA Polymerase EC 2.7.7.7
POL31 protein, S cerevisiae EC 2.7.7.7

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5623-5636

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM118020
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118129
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 ES065070
Pays : United States

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Denis A Kiktev (DA)

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
ORCID: 0000-0002-8763-6401

Margaret Dominska (M)

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

Tony Zhang (T)

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

Joseph Dahl (J)

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

Elena I Stepchenkova (EI)

Department of Genetics and Biotechnology, Saint-Petersburg State University, St. Petersburg, Russia.
Vavilov Institute of General Genetics, Saint-Petersburg Branch, Russian Academy of Sciences, St. Petersburg, Russia.

Piotr Mieczkowski (P)

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.

Peter M Burgers (PM)

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Scott Lujan (S)

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

Adam Burkholder (A)

Office of Environmental Science Cyberinfrastructure, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

Thomas A Kunkel (TA)

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

Thomas D Petes (TD)

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
ORCID: 0000-0003-4890-8002

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Domaine catalytique › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › DNA nucleotidyltransferases › DNA-directed DNA polymerase › DNA polymerase III › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Phénomènes génétiques › Réparation de l'ADN › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › DNA nucleotidyltransferases › DNA-directed DNA polymerase › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Protéines à fer non hème › Ferrosulfoprotéines › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Protéines de Saccharomyces cerevisiae › The fidelity of DNA replication, particularly...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › The fidelity of DNA replication, particularly...