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

Publication ,  Journal Article
Kiktev, DA; Dominska, M; Zhang, T; Dahl, J; Stepchenkova, EI; Mieczkowski, P; Burgers, PM; Lujan, S; Burkholder, A; Kunkel, TA; Petes, TD
Published in: Nucleic Acids Res
June 4, 2021

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.

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Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

June 4, 2021

Volume

49

Issue

10

Start / End Page

5623 / 5636

Location

England

Related Subject Headings

  • Transcription Factors
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Protein Binding
  • Iron-Sulfur Proteins
  • Developmental Biology
  • DNA-Directed DNA Polymerase
  • DNA Replication
  • DNA Repair
  • DNA Polymerase III
 

Citation

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Kiktev, D. A., Dominska, M., Zhang, T., Dahl, J., Stepchenkova, E. I., Mieczkowski, P., … Petes, T. D. (2021). The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ. Nucleic Acids Res, 49(10), 5623–5636. https://doi.org/10.1093/nar/gkab371
Kiktev, Denis A., Margaret Dominska, Tony Zhang, Joseph Dahl, Elena I. Stepchenkova, Piotr Mieczkowski, Peter M. Burgers, et al. “The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ.Nucleic Acids Res 49, no. 10 (June 4, 2021): 5623–36. https://doi.org/10.1093/nar/gkab371.
Kiktev DA, Dominska M, Zhang T, Dahl J, Stepchenkova EI, Mieczkowski P, et al. The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ. Nucleic Acids Res. 2021 Jun 4;49(10):5623–36.
Kiktev, Denis A., et al. “The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ.Nucleic Acids Res, vol. 49, no. 10, June 2021, pp. 5623–36. Pubmed, doi:10.1093/nar/gkab371.
Kiktev DA, Dominska M, Zhang T, Dahl J, Stepchenkova EI, Mieczkowski P, Burgers PM, Lujan S, Burkholder A, Kunkel TA, Petes TD. The fidelity of DNA replication, particularly on GC-rich templates, is reduced by defects of the Fe-S cluster in DNA polymerase δ. Nucleic Acids Res. 2021 Jun 4;49(10):5623–5636.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

June 4, 2021

Volume

49

Issue

10

Start / End Page

5623 / 5636

Location

England

Related Subject Headings

  • Transcription Factors
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Protein Binding
  • Iron-Sulfur Proteins
  • Developmental Biology
  • DNA-Directed DNA Polymerase
  • DNA Replication
  • DNA Repair
  • DNA Polymerase III