Evidence map›Paper›PMID 23268450›Full record

ArticleNucleic acids research2013

Replication of a carcinogenic nitropyrene DNA lesion by human Y-family DNA polymerase.

Kevin N Kirouac, Ashis K Basu, Hong Ling

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 2 countries.

Kevin N KirouacDepartment of Biochemistry, Medical Sciences Building 334, University of Western Ontario, London, ON N6A 5C1, Canada.
Ashis K Basu
Hong Ling
University of Connecticut · US

Funding

BIOLOGICAL EFFECTS OF DNA ADDUCTS FORMED BY NITROPYRENESR01ES009127 · NIEHS · UNIVERSITY OF CONNECTICUT STORRS · PI BASU, ASHIS K, SUO, ZUCAI · 1998 to 2014
$3.5M
Biological Effects of DNA Adducts Formed by Nitroaromatic CompoundsR56ES009127 · NIEHS · UNIVERSITY OF CONNECTICUT STORRS · PI BASU, ASHIS K, SUO, ZUCAI · 2009 to 2009
$393k
CIHR MOP93590NIEHS NIH HHS ES09127NIEHS NIH HHS R01 ES009127
6 · The paper itself

Abstract

Nitrated polycyclic aromatic hydrocarbons are common environmental pollutants, of which many are mutagenic and carcinogenic. 1-Nitropyrene is the most abundant nitrated polycyclic aromatic hydrocarbon, which causes DNA damage and is carcinogenic in experimental animals. Error-prone translesion synthesis of 1-nitropyrene-derived DNA lesions generates mutations that likely play a role in the etiology of cancer. Here, we report two crystal structures of the human Y-family DNA polymerase iota complexed with the major 1-nitropyrene DNA lesion at the insertion stage, incorporating either dCTP or dATP nucleotide opposite the lesion. Polι maintains the adduct in its active site in two distinct conformations. dCTP forms a Watson-Crick base pair with the adducted guanine and excludes the pyrene ring from the helical DNA, which inhibits replication beyond the lesion. By contrast, the mismatched dATP stacks above the pyrene ring that is intercalated in the helix and achieves a productive conformation for misincorporation. The intra-helical bulky pyrene mimics a base pair in the active site and facilitates adenine misincorporation. By structure-based mutagenesis, we show that the restrictive active site of human polη prevents the intra-helical conformation and A-base misinsertions. This work provides one of the molecular mechanisms for G to T transversions, a signature mutation in human lung cancer.

Indexed as

CarcinogensDeoxyadenine NucleotidesDeoxycytosine NucleotidesDeoxyguanosineDNA AdductsDNA-Directed DNA PolymeraseDNA Polymerase iotaDNA ReplicationHumansModels, MolecularPyrenesY-Family DNA Polymerases2'-deoxyadenosine triphosphate2'-deoxycytidine 5'-triphosphateCarcinogensDeoxyadenine NucleotidesDeoxycytosine NucleotidesDeoxyguanosineDNA AdductsDNA-Directed DNA PolymeraseDNA Polymerase iotaN-(deoxyguanosine-8-yl)-1-aminopyrenePOLI protein, humanPyrenesRad30 proteinY-Family DNA Polymerases

Identifiers

PMID23268450
PMCPMC3561991
OpenAlexW2084583391

What OpenQuestion holds

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LicenceCC BY-NC
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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.