ArticleLife science alliance2019
Human DNA polymerase delta requires an iron-sulfur cluster for high-fidelity DNA synthesis.
Article in Life science alliance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Interpreting the effects of DNA polymerase variants at the structural level.Molecular oncology · 2026Article
- Iron-sulfur cofactors in nucleic acid metabolism and protein synthesis: Assembly, delivery, and putative roles in cellular and viral systems.The Journal of biological chemistry · 2026Review
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- The genetic and biochemical basis of human leading strand synthesis.Nature communications · 2025Article
- Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1.Nature communications · 2025Article
- Control of Replication Stress Response by Cytosolic Fe-S Cluster Assembly (CIA) Machinery.Cells · 2025Review
- Review
- Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes.Nature communications · 2024Article
- Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis.Nucleic acids research · 2023Article
- Maintenance of genome integrity by the late-acting cytoplasmic iron-sulfur assembly (CIA) complex.Frontiers in genetics · 2023Review
- 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 research · 2021Article
- Diet as a Potential Moderator for Genome Stability and Immune Response in Pediatric Leukemia.Cancers · 2021Review
- Biogenesis of Iron-Sulfur Clusters and Their Role in DNA Metabolism.Frontiers in cell and developmental biology · 2021Review
- Iron: An Essential Element of Cancer Metabolism.Cells · 2020Review
- The iron-sulphur cluster in human DNA2 is required for all biochemical activities of DNA2.Communications biology · 2020Article
- Cancer-associated mutations in the iron-sulfur domain of FANCJ affect G-quadruplex metabolism.PLoS genetics · 2020Article
- The iron-sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activation.Life science alliance · 2020Article
- Structure of the processive human Pol δ holoenzyme.Nature communications · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication of eukaryotic genomes relies on the family B DNA polymerases Pol α, Pol δ, and Pol ε. All of these enzymes coordinate an iron-sulfur (FeS) cluster, but the function of this cofactor has remained largely unclear. Here, we show that the FeS cluster in the catalytic subunit of human Pol δ is coordinated by four invariant cysteines of the C-terminal CysB motif. FeS cluster loss causes a partial destabilisation of the four-subunit enzyme, a defect in double-stranded DNA binding, and compromised polymerase and exonuclease activities. Importantly, complex stability, DNA binding, and enzymatic activities are restored in the presence of proliferating cell nuclear antigen. We further show that also more subtle changes to the FeS cluster-binding pocket that do not abolish FeS cluster binding can have repercussions on the distant exonuclease domain and render the enzyme error prone. Our data hence suggest that the FeS cluster in human Pol δ is an important co-factor that despite its C-terminal location has an impact on both DNA polymerase and exonuclease activities, and can influence the fidelity of DNA synthesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.