Evidence map›Paper›PMID 15746000›Full record

ArticleNucleic acids research2005

Cadmium inhibits mismatch repair by blocking the ATPase activity of the MSH2-MSH6 complex.

Sreeparna Banerjee, Hernan Flores-Rozas

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
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  8. The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

2 authors at 1 institution in 2 countries.

Sreeparna BanerjeeInstitute of Molecular Medicine and Genetics, Medical College of Georgia 1120 15th Street, Augusta, GA 30912, USA.
Hernan Flores-Rozas
Institute of Molecular Medicine · IN

Funding

Links between Mismatch Repair and ReplicationR01GM068536 · NIGMS · MEDICAL COLLEGE OF GEORGIA (MCG) · PI FLORES-ROZAS, HERNAN A · 2003 to 2005
$708k
NIGMS NIH HHS GM068536NIGMS NIH HHS R01 GM068536
6 · The paper itself

Abstract

Cadmium (Cd2+) is a known carcinogen that inactivates the DNA mismatch repair (MMR) pathway. In this study, we have tested the effect of Cd2+ exposure on the enzymatic activity of the mismatch binding complex MSH2-MSH6. Our results indicate that Cd2+ is highly inhibitory to the ATP binding and hydrolysis activities of MSH2-MSH6, and less inhibitory to its DNA mismatch binding activity. The inhibition of the ATPase activity appears to be dose and exposure time dependent. However, the inhibition of the ATPase activity by Cd2+ is prevented by cysteine and histidine, suggesting that these residues are essential for the ATPase activity and are targeted by Cd2+. A comparison of the mechanism of inhibition with N-ethyl maleimide, a sulfhydryl group inhibitor, indicates that this inhibition does not occur through direct inactivation of sulfhydryl groups. Zinc (Zn2+) does not overcome the direct inhibitory effect of Cd2+ on the MSH2-MSH6 ATPase activity in vitro. However, the increase in the mutator phenotype of yeast cells exposed to Cd2+ was prevented by excess Zn2+, probably by blocking the entry of Cd2+ into the cell. We conclude that the inhibition of MMR by Cd2+ is through the inactivation of the ATPase activity of the MSH2-MSH6 heterodimer, resulting in a dominant negative effect and causing a mutator phenotype.

Indexed as

Adenosine TriphosphatasesAdenosine TriphosphateAmino AcidsBase Pair MismatchCadmiumDNADNA-Binding ProteinsDNA RepairEthylmaleimideMutationMutS Homolog 2 ProteinPhenotypeSaccharomyces cerevisiae ProteinsSulfhydryl ReagentsYeastsZincAdenosine TriphosphatasesAdenosine TriphosphateAmino AcidsCadmiumDNADNA-Binding ProteinsEthylmaleimideMSH2 protein, S cerevisiaeMSH6 protein, S cerevisiaeMutS Homolog 2 ProteinSaccharomyces cerevisiae ProteinsSulfhydryl ReagentsZinc

Identifiers

PMID15746000
PMCPMC552968
OpenAlexW2162614299

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.