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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kiktev, DA; Dominska, M; Zhang, T; Dahl, J; Stepchenkova, EI; Mieczkowski, P; Burgers, PM; Lujan, S; Burkholder, A; Kunkel, TA; Petes, TD

Published Date

  • June 4, 2021

Published In

Volume / Issue

  • 49 / 10

Start / End Page

  • 5623 - 5636

PubMed ID

  • 34019669

Pubmed Central ID

  • PMC8191807

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkab371

Language

  • eng

Conference Location

  • England