Arsenite Interacts Selectively with Zinc Finger Proteins Containing C3H1 or C4 Motifs
Open accessAbstract
Arsenic inhibits DNA repair and enhances the genotoxicity of DNA-damaging agents such as benzo[a]pyrene and ultraviolet radiation. Arsenic interaction with DNA repair proteins containing functional zinc finger motifs is one proposed mechanism to account for these observations. Here, we report that arsenite binds to both CCHC DNA-binding zinc fingers of the DNA repair protein PARP-1 (poly(ADP-ribose) polymerase-1). Furthermore, trivalent arsenite coordinated with all three cysteine residues as demonstrated by MS/MS. MALDI-TOF-MS analysis of peptides harboring site-directed substitutions of cysteine with histidine residues within the PARP-1 zinc finger revealed that arsenite bound to peptides containing three or four cysteine residues, but not to peptides with two cysteines, demonstrating arsenite binding selectivity. This finding was not unique to PARP-1; arsenite did not bind to a peptide representing the CCHH zinc finger of the DNA repair protein aprataxin, but did bind to an aprataxin peptide mutated to a CCHC zinc finger. To investigate the impact of arsenite on PARP-1 zinc finger function, we measured the zinc content and DNA-binding capacity of PARP-1 immunoprecipitated from arsenite-exposed cells. PARP-1 zinc content and DNA binding were decreased by 76 and 80%, respectively, compared with protein isolated from untreated cells. We observed comparable decreases in zinc content for XPA (xeroderma pigmentosum group A) protein (CCCC zinc finger), but not SP-1 (specificity protein-1) or aprataxin (CCHH zinc finger). These findings demonstrate that PARP-1 is a direct molecular target of arsenite and that arsenite interacts selectively with zinc finger motifs containing three or more cysteine residues.
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Genotoxicity occurs because ROS reacts with both deoxyribose and bases in DNA, causing base lesions and strand breaks.
“Genotoxicity occurs since ROS reacts with both deoxyribose and bases in DNA, causing base lesions and strand breaks.”
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S-nitrosation on zinc finger motif of PARP-1 as a mechanism of DNA repair inhibition by arsenite
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Arsenite Exposure Displaces Zinc from ZRANB2 Leading to Altered Splicing
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Once Upon a Mine: The Legacy of Uranium on the Navajo Nation
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Self-citationDouble-Edged Effects of Arsenic Compounds: Anticancer and Carcinogenic Effects
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Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue
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Self-citationArsenic is a potent co-mutagen of ultraviolet light
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Self-citationMonomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells
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Autophagy as the effector and player in DNA damage response of cells to genotoxicants
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Self-citation
- Authors
- Zhou, X., Sun, X., Cooper, K. L., Wang, F., Liu, K. J., & Hudson, L. G.
- Affiliations
- University of New Mexico (US)
- Corresponding author
- Liu, Ke Jian
- Hudson, Laurie G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 286
- Issue
- 26
- Pages
- 22855-22863
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3123053
- OpenAlex
- W1986093310
- Cited by
- 177
- References
- 43
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 12 · 2021: 7 · 2020: 17 · 2019: 8 · 2018: 12 · 2017: 16 · 2016: 14 · 2015: 22 · 2014: 14 · 2013: 13 · 2012: 12
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA118100)
- National Cancer Institute (P30CA118100)
- National Institute of Environmental Health Sciences (R01ES15826-03S1, R01ES15826, R01ES015826)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
- Keywords
- arsenite, zinc finger proteins, PARP1, CCHC zinc finger, aprataxin, XPA, Sp1, cysteine residues, DNA repair proteins, genotoxicity
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Cell Line, DNA-Binding Proteins, Humans, Mutation, Nuclear Proteins, Peptides, Poly(ADP-ribose) Polymerases, Protein Binding, Teratogens, Zinc Fingers, Arsenites
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