Evidence map›Paper›PMID 18946034›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2008

Human DNA polymerase eta activity and translocation is regulated by phosphorylation.

Yih-Wen Chen, James E Cleaver, Zafer Hatahet, Richard E Honkanen, Jang-Yang Chang, Yun Yen, Kai-Ming Chou

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

42 citing papers in PubMed, 60 citations in OpenAlex.

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  8. The 6-4 photoproduct is the trigger of UV-induced replication blockage and ATR activation.Proceedings of the National Academy of Sciences of the United States of America · 2020
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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

7 authors at 7 institutions in 2 countries.

Yih-Wen ChenDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202.
James E Cleaver
Zafer Hatahet
Richard E Honkanen
Jang-Yang Chang
Yun Yen
Kai-Ming Chou
City Of Hope National Medical Center · USIndiana University – Purdue University Indianapolis · USIndiana University School of MedicineNational Health Research Institutes · TWNorthwestern State University · USUniversity of California, San Francisco · USUniversity of South Alabama · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7M
MECHANISMS OF TUMOR PROMOTION AND CARCINOGENESISR01CA060750 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI HONKANEN, RICHARD E · 1999 to 2009
$2.5M
DNA Damage and Neurodegeneration in Cockayne SyndromeR01NS052781 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CLEAVER, JAMES E · 2006 to 2009
$1.4M
DNA Lesion Bypass Polymerases and Therapeutic CompoundsR01CA112446 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI CHOU, KAI-MING · 2007 to 2012
$1.1M
MECHANISMS OF TUMOR PROMOTION AND CARCINOGENESISR29CA060750 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI HONKANEN, RICHARD E · 1994 to 1998
–
NCI NIH HHS CA112446NCI NIH HHS CA60750NCI NIH HHS CA82103NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA060750NCI NIH HHS R01 CA112446NINDS NIH HHS NS052781NINDS NIH HHS R01 NS052781
6 · The paper itself

Abstract

Human DNA polymerase eta (pol eta) can replicate across UV-induced pyrimidine dimers, and defects in the gene encoding pol eta result in a syndrome called xeroderma pigmentosum variant (XP-V). XP-V patients are prone to the development of cancer in sun-exposed areas, and cells derived from XP-V patients demonstrate increased sensitivity to UV radiation and a higher mutation rate compared with wild-type cells. pol eta has been shown to replicate across a wide spectrum of DNA lesions introduced by environmental or chemotherapeutic agents, or during nucleotide starvation, suggesting that the biological roles for pol eta are not limited to repair of UV-damaged DNA. The high error rate of pol eta requires that its intracellular activity be tightly regulated. Here, we show that the phosphorylation of pol eta increased after UV irradiation, and that treatment with caffeine, siRNA against ATR, or an inhibitor of PKC (calphostin C), reduced the accumulation of pol eta at stalled replication forks after UV irradiation or treatment with cisplatin and gemcitabine. Site-specific mutagenesis (S587A and T617A) of pol eta at two putative PKC phosphorylation sites located in the protein-protein interaction domain prevented nuclear foci formation induced by UV irradiation or treatment with gemcitabine/cisplatin. In addition, XP-V cell lines stably expressing either the S587A or T617A mutant form of pol eta were more sensitive to UV radiation and gemcitabine/cisplatin than control cells expressing wild-type pol eta. These results suggest that phosphorylation is one mechanism by which the cellular activity of pol eta is regulated.

Indexed as

DNA ReplicationAtaxia Telangiectasia Mutated ProteinsCaffeineCell Cycle ProteinsCell LineDNA DamageDNA-Directed DNA PolymeraseHumansMutation, MissensePhosphorylationProtein Kinase CProtein Serine-Threonine KinasesRNA, Small InterferingUltraviolet RaysY-Family DNA PolymerasesAtaxia Telangiectasia Mutated ProteinsATR protein, humanCaffeineCell Cycle ProteinsDNA-Directed DNA PolymeraseProtein Kinase CProtein Serine-Threonine KinasesRad30 proteinRNA, Small InterferingY-Family DNA Polymerases

Identifiers

PMID18946034
PMCPMC2575462
OpenAlexW2092963627

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.