Interference by toxic metal compounds with isolated zinc finger DNA repair proteins

Asmuss, Monika; Mullenders, Leon H.F.; Hartwig, Andrea

doi:10.1016/s0378-4274(99)00273-8

Cited by 114 publications

(70 citation statements)

References 16 publications

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“…Our results showing disruption of H3K9me2 domain boundaries at weak CTCF-binding sites suggest a role for CTCF in H3K9me2 domain maintenance. Previous studies have shown that Ni interaction with Zn finger proteins results in inhibition of DNA binding and alteration of DNA-binding specificity (49,50). Interestingly, our results suggest that nickel at noncytotoxic concentrations preferentially inhibits binding of CTCF to the weaker binding sequences (Fig.…”

Section: Discussionsupporting

confidence: 55%

Epigenetic dysregulation by nickel through repressive chromatin domain disruption

Jose

Jagannathan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Investigations into the genomic landscape of histone modifications in heterochromatic regions have revealed histone H3 lysine 9 dimethylation (H3K9me2) to be important for differentiation and maintaining cell identity. H3K9me2 is associated with gene silencing and is organized into large repressive domains that exist in close proximity to active genes, indicating the importance of maintenance of proper domain structure. Here we show that nickel, a nonmutagenic environmental carcinogen, disrupted H3K9me2 domains, resulting in the spreading of H3K9me2 into active regions, which was associated with gene silencing. We found weak CCCTC-binding factor (CTCF)-binding sites and reduced CTCF binding at the Ni-disrupted H3K9me2 domain boundaries, suggesting a loss of CTCF-mediated insulation function as a potential reason for domain disruption and spreading. We furthermore show that euchromatin islands, local regions of active chromatin within large H3K9me2 domains, can protect genes from H3K9me2-spreadingassociated gene silencing. These results have major implications in understanding H3K9me2 dynamics and the consequences of chromatin domain disruption during pathogenesis.insulator | nickel toxicity | nickel carcinogenesis

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Section: Discussionsupporting

confidence: 55%

Epigenetic dysregulation by nickel through repressive chromatin domain disruption

Jose

Jagannathan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Regarding XPA, arsenic and lead did not decrease its binding to a UVirradiated oligoucleotide, whereas cadmium, cobalt and nickel interfere with its DNA binding ability. A simultaneous treatment with zinc largely prevented this inhibition (Asmuß et al, 2000). Structural investigations by different spectroscopic methods revealed a tetrahedrally co-ordination of all three metal ions with no major distortion of XPA while for cadmium an increased Cd-S bond length was observed.…”

Section: Mechanism Of Actionmentioning

confidence: 93%

“…In support of this assumption, in cellfree systems lead has been shown to reduce DNA binding of transcription factors (TFIIIA) and Sp1 (Huang et al 2004). No impact was however described on the zinc-containing DNA repair proteins Fpg or XPA (Asmuß et al 2000).…”

Section: Leadmentioning

confidence: 98%

“…Finally lead, element with high affinities to thiolates, can replace zinc in zinc finger domains and disrupt their fold. Arsenic too is known to have a high affinity to -SH groups and it is demonstrated by arsenic-mediated repair inhibition not related with a direct mechanism of one or more specific repair proteins, but rather with changes in gene expression and/or signal transduction (Asmuß et al, 2000). proteins.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…De Boeck et al, (1998) assessed the interference of cobalt compounds with the repair of primarily-induced DNA damage and showed that cobalt was able to cause persistence of methylmethanesulphonate-induced DNA lesions by interference its repair. In particular, cobalt inhibited the Xeroderma pigmentosum group A (XPA) protein, a zinc finger protein involved in nucleotide excision repair (Asmuß et al 2000) where it substituted for the zinc ion (Kopera et al 2004). Cobalt at low, non-cytotoxic concentrations interferes with the incision step of UV-induced DNA repair, but the removal of lesions may not be uniformly affected (Kasten et al, 1997).…”

Section: Cobaltmentioning

confidence: 99%

See 2 more Smart Citations

Interactions by Carcinogenic Metal Compounds with DNA Repair Processes

Catalani¹,

Apostoli²

2011

Selected Topics in DNA Repair

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Metallionen zwischen Essenzialität und Toxizität

Hartwig

2000

Chemie in unserer Zeit

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Metallionen spielen eine wichtige Rolle bei vielen biochemischen Prozessen, gleichzeitig sind aber auch toxische Wirkungen bekannt. Welche Strategien verwenden Lebewesen, um essenzielle Funktionen aufrechtzuerhalten und sich vor toxischen Reaktionen zu schützen? Welche Rolle spielt die Wechselwirkung zwischen toxischen und essenziellen Metallionen bei der Krebsentstehung? M etallionen und Metallverbindungen sind ubiquitär in der Umwelt vorhanden. Viele von ihnen, darunter Calcium, Magnesium, Zink, Cobalt, Nickel, Mangan und Eisen, sind essenzielle Bestandteile von biologischen Systemen. Sie vermitteln den Sauerstofftransport und -metabolismus, katalysieren Elektronenübertragungsreaktionen, sind an der Signalübertragung beteiligt und stabilisieren die Struktur von Makromolekülen. Zudem vermitteln sie aber auch das Zusammenwirken der Makromoleküle untereinander, wie Zink in Zinkfingerstrukturen, die als häufiges Motiv bei DNA-bindenden Proteinen nachgewiesen wurden. Allerdings haben sich Verbindungen von Arsen, Beryllium, Cadmium, Nickel, Chrom, Cobalt und Blei als krebserzeugend beim Menschen und/oder im Tierversuch erwiesen; einige Quecksilberverbindungen sind extrem toxisch (Tabelle 1). Auffällig ist, dass toxische und sogar kanzerogene Wirkungen keineswegs auf nichtessenzielle Metalle beschränkt sind, sondern auch bei essenziellen Elementen beobachtet werden. Die oftmals enge Verknüpfung zwischen essenzieller und toxischer Wirkung wird besonders bei Übergangsmetallen wie Eisen und Kupfer [1] deutlich. Eine ihrer essenziellen biologischen Funktionen besteht darin, Ein-Elektronen-Übergänge zu katalysieren; genau diese Fähigkeit der Übergangsmetallionen kann aber auch zu toxischen Reaktionen führen, indem reaktive Sauerstoffspezies generiert werden, die in der Folge zelluläre Makromoleküle schädigen können.

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Interference by toxic metal compounds with isolated zinc finger DNA repair proteins

Cited by 114 publications

References 16 publications

Epigenetic dysregulation by nickel through repressive chromatin domain disruption

Epigenetic dysregulation by nickel through repressive chromatin domain disruption

Interactions by Carcinogenic Metal Compounds with DNA Repair Processes

Metallionen zwischen Essenzialität und Toxizität

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