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DNA polymerase kappa protects human cells against MMC-induced genotoxicity through error-free translesion DNA synthesis

Overview of attention for article published in Genes and Environment, January 2017
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Title
DNA polymerase kappa protects human cells against MMC-induced genotoxicity through error-free translesion DNA synthesis
Published in
Genes and Environment, January 2017
DOI 10.1186/s41021-016-0067-3
Pubmed ID
Authors

Yuki Kanemaru, Tetsuya Suzuki, Akira Sassa, Kyomu Matsumoto, Noritaka Adachi, Masamitsu Honma, Satoshi Numazawa, Takehiko Nohmi

Abstract

Interactions between genes and environment are critical factors for causing cancer in humans. The genotoxicity of environmental chemicals can be enhanced via the modulation of susceptible genes in host human cells. DNA polymerase kappa (Pol κ) is a specialized DNA polymerase that plays an important role in DNA damage tolerance through translesion DNA synthesis. To better understand the protective roles of Pol κ, we previously engineered two human cell lines either deficient in expression of Pol κ (KO) or expressing catalytically dead Pol κ (CD) in Nalm-6-MSH+ cells and examined cytotoxic sensitivity against various genotoxins. In this study, we set up several genotoxicity assays with cell lines possessing altered Pol κ activities and investigated the protective roles of Pol κ in terms of genotoxicity induced by mitomycin C (MMC), a therapeutic agent that induces bulky DNA adducts and crosslinks in DNA. We introduced a frameshift mutation in one allele of the thymidine kinase (TK) gene of the KO, CD, and wild-type Pol κ cells (WT), thereby establishing cell lines for the TK gene mutation assay, namely TK+/- cells. In addition, we formulated experimental conditions to conduct chromosome aberration (CA) and sister chromatid exchange (SCE) assays with cells. By using the WT TK+/- and KO TK+/- cells, we assayed genotoxicity of MMC. In the TK gene mutation assay, the cytotoxic and mutagenic sensitivities of KO TK+/- cells were higher than those of WT TK+/- cells. MMC induced loss of heterozygosity (LOH), base pair substitutions at CpG sites and tandem mutations at GpG sites in both cell lines. However, the frequencies of LOH and base substitutions at CpG sites were significantly higher in KO TK+/- cells than in WT TK+/- cells. MMC also induced CA and SCE in both cell lines. The KO TK+/- cells displayed higher sensitivity than that displayed by WT TK+/- cells in the SCE assay. These results suggest that Pol κ is a modulating factor for the genotoxicity of MMC and also that the established cell lines are useful for evaluating the genotoxicity of chemicals from multiple endpoints in different genetic backgrounds of Pol κ.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 16%
Student > Ph. D. Student 3 16%
Student > Postgraduate 2 11%
Professor 1 5%
Researcher 1 5%
Other 1 5%
Unknown 8 42%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 32%
Agricultural and Biological Sciences 2 11%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Chemistry 1 5%
Unknown 9 47%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 January 2017.
All research outputs
#17,470,670
of 21,619,833 outputs
Outputs from Genes and Environment
#60
of 101 outputs
Outputs of similar age
#311,479
of 421,550 outputs
Outputs of similar age from Genes and Environment
#12
of 17 outputs
Altmetric has tracked 21,619,833 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 421,550 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.