Evidence map›Paper›PMID 21824916›Full record

ArticleNucleic acids research2011

Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage.

Angela E Zolner, Ismail Abdou, Ruiqiong Ye, Rajam S Mani, Mesfin Fanta, Yaping Yu, Pauline Douglas, Nasser Tahbaz, Shujuan Fang, Tracey Dobbs and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

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  20. Chromosome instability syndromes.Nature reviews. Disease primers · 2019
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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

15 authors at 3 institutions in 2 countries.

Angela E ZolnerDepartment of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Ismail Abdou
Ruiqiong Ye
Rajam S Mani
Mesfin Fanta
Yaping Yu
Pauline Douglas
Nasser Tahbaz
Shujuan Fang
Tracey Dobbs
Chen Wang
Nick Morrice
Michael J Hendzel
Michael Weinfeld
Susan P Lees-Miller
University of Alberta · CAUniversity of Calgary · CAMRC Protein Phosphorylation and Ubiquitylation Unit · GB

Funding

Canadian Institutes of Health Research 13639Canadian Institutes of Health Research 15385
6 · The paper itself

Abstract

Human polynucleotide kinase/phosphatase (PNKP) is a dual specificity 5'-DNA kinase/3'-DNA phosphatase, with roles in base excision repair, DNA single-strand break repair and non-homologous end joining (NHEJ); yet precisely how PNKP functions in the repair of DNA double strand breaks (DSBs) remains unclear. We demonstrate that PNKP is phosphorylated by the DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Ionizing radiation (IR)-induced phosphorylation of cellular PNKP on S114 was ATM dependent, whereas phosphorylation of PNKP on S126 required both ATM and DNA-PK. Inactivation of DNA-PK and/or ATM led to reduced PNKP at DNA damage sites in vivo. Cells expressing PNKP with alanine or aspartic acid at serines 114 and 126 were modestly radiosensitive and IR enhanced the association of PNKP with XRCC4 and DNA ligase IV; however, this interaction was not affected by mutation of PNKP phosphorylation sites. Purified PNKP protein with mutation of serines 114 and 126 had decreased DNA kinase and DNA phosphatase activities and reduced affinity for DNA in vitro. Together, our results reveal that IR-induced phosphorylation of PNKP by ATM and DNA-PK regulates PNKP function at DSBs.

Indexed as

DNA Breaks, Double-StrandedAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Repair EnzymesHeLa CellsHumansMutationPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein Serine-Threonine KinasesRadiation, IonizingRadiation ToleranceSerineTumor Suppressor ProteinsAtaxia Telangiectasia Mutated ProteinsATM protein, humanCell Cycle ProteinsDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Repair EnzymesPhosphotransferases (Alcohol Group Acceptor)PNKP protein, humanProtein Serine-Threonine KinasesSerineTumor Suppressor ProteinsXRCC4 protein, human

Identifiers

PMID21824916
PMCPMC3241656
OpenAlexW1996131612

What OpenQuestion holds

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LicenceCC BY-NC
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.