An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ε

Rinku Jain, Eva S. Vanamee, Boris G. Dzikovski, Angeliki Buku, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

DNA polymerase ε (Polε) is a multi-subunit polymerase that contributes to genomic stability via its roles in leading strand replication and the repair of damaged DNA. Polε from Saccharomyces cerevisiae is composed of four subunits - Pol2, Dpb2, Dpb3, and Dpb4. Here, we report the presence of a [Fe-S] cluster directly within the active polymerase domain of Pol2 (residues 1-1187). We show that binding of the [Fe-S] cluster is mediated by cysteines in an insertion (Pol2ins) that is conserved in Pol2 orthologs but is absent in the polymerase domains of Polα, Polδ, and Polζ. We also show that the [Fe-S] cluster is required for Pol2 polymerase activity but not for its exonuclease activity. Collectively, our work suggests that Polε is perhaps more sensitive than other DNA polymerases to changes in oxidative stress in eukaryotic cells.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalJournal of Molecular Biology
Volume426
Issue number2
DOIs
StatePublished - Jan 23 2014

Fingerprint

DNA-Directed DNA Polymerase
Sulfur
Iron
Yeasts
Exonucleases
Genomic Instability
Eukaryotic Cells
DNA Repair
Cysteine
Saccharomyces cerevisiae
Oxidative Stress

Keywords

  • DNA polymerase
  • DNA repair
  • DNA replication
  • Fe-S cluster
  • oxidative stress

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Jain, R., Vanamee, E. S., Dzikovski, B. G., Buku, A., Johnson, R. E., Prakash, L., ... Aggarwal, A. K. (2014). An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ε. Journal of Molecular Biology, 426(2), 301-308. https://doi.org/10.1016/j.jmb.2013.10.015

An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ε. / Jain, Rinku; Vanamee, Eva S.; Dzikovski, Boris G.; Buku, Angeliki; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Journal of Molecular Biology, Vol. 426, No. 2, 23.01.2014, p. 301-308.

Research output: Contribution to journalArticle

Jain, R, Vanamee, ES, Dzikovski, BG, Buku, A, Johnson, RE, Prakash, L, Prakash, S & Aggarwal, AK 2014, 'An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ε', Journal of Molecular Biology, vol. 426, no. 2, pp. 301-308. https://doi.org/10.1016/j.jmb.2013.10.015
Jain, Rinku ; Vanamee, Eva S. ; Dzikovski, Boris G. ; Buku, Angeliki ; Johnson, Robert E. ; Prakash, Louise ; Prakash, Satya ; Aggarwal, Aneel K. / An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ε. In: Journal of Molecular Biology. 2014 ; Vol. 426, No. 2. pp. 301-308.
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