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Zinc Finger Proteins as Potential Targets for Toxic Metal Ions: Differential Effects on Structure and Function
Abstract
Zinc finger structures are frequently found in transcription factors and DNA repair proteins, mediating DNA-protein and protein-protein binding. As low concentrations of transition metal compounds, including those of cadmium, nickel, and cobalt, have been shown to interfere with DNA transcription and repair, several studies have been conducted to elucidate potential interactions of toxic metal ions with zinc-binding protein domains. Various effects have been identified, including the displacement of zinc, e.g., by cadmium or cobalt, the formation of mixed complexes, incomplete coordination of toxic metal ions, as well as the oxidation of cysteine residues within the metal-binding domain. Besides the number of cysteine and/or histidine ligands, unique structural features of the respective protein under investigation determine whether or not zinc finger structures are disrupted by one or more transition metals. As improper folding of zinc finger domains is mostly associated with the loss of correct protein function, disruption of zinc finger structures may result in interference with manifold cellular processes involved in gene expression, growth regulation, and maintenance of the genomic integrity.
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“As induces genotoxicity by generating ROS in similar fashion as cytotoxicity [103].”
From Arsenic Contamination of Groundwater: A Review of Sources, Prevalence, Health Risks, and Strategies for Mitigation (2014) · cites this paper as [103]
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“As interacts with DNA repair proteins possessing functional zinc finger motifs, which are involved in transcription, DNA repair proteins, and DNA-protein and protein-protein binding [105, 106].”
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Metadata
- Authors
- Hartwig, A.
- Affiliations
- Karlsruhe Institute of Technology (DE)
- Corresponding author
- Hartwig, Andrea
- ORCID
- Hartwig, Andrea
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2001-08
- Volume
- 3
- Issue
- 4
- Pages
- 625-634
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W1983045184
- Cited by
- 269
- References
- 63
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 5 · 2023: 12 · 2022: 7 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 14 · 2017: 8 · 2016: 13 · 2015: 15 · 2014: 15 · 2013: 12 · 2012: 14
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Keywords
- zinc finger proteins, toxic metal ions, cadmium, nickel, cobalt, metal ion binding, zinc displacement, heterometallic complexes, cysteine oxidation, histidine ligands, protein misfolding, transcription factors, DNA repair proteins
- MeSH terms
- Binding, Competitive, DNA, DNA Repair, Humans, Metals, Neoplasm Proteins, Protein Binding, Protein Conformation, Structure-Activity Relationship, Transcription Factors, Transcription, Genetic, Xeroderma Pigmentosum, Zinc Fingers, Protein Folding, Denys-Drash Syndrome
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