Evidence map›Paper›PMID 24844881›Full record

ArticleBioscience reports2014

Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis.

Pauline Douglas, Ruiqiong Ye, Laura Trinkle-Mulcahy, Jessica A Neal, Veerle De Wever, Nick A Morrice, Katheryn Meek, Susan P Lees-Miller

Open access · goldAbstract read
In one paragraph

Article in Bioscience reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

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  17. Frontiers in molecular biosciences · 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

8 authors at 2 institutions in 1 country.

Pauline Douglas*Departments of Biochemistry & Molecular Biology and Oncology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.
Ruiqiong Ye*Departments of Biochemistry & Molecular Biology and Oncology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.
Laura Trinkle-Mulcahy†Department of Cellular & Molecular Medicine and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada, K1H 8M5.
Jessica A Neal‡Departments of Pathobiology & Diagnostic Investigation, and Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan, U.S.A.
Veerle De Wever§Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 4N1.
Nick A Morrice∥Beatson Institute for Cancer Research, Glasgow G61 1BD Scotland, U.K.
Katheryn Meek‡Departments of Pathobiology & Diagnostic Investigation, and Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan, U.S.A.
Susan P Lees-Miller*Departments of Biochemistry & Molecular Biology and Oncology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.
University of Calgary · CAUniversity of Ottawa · CA

Funding

Relevant Targets of the DNA Dependent Protein KinaseR01AI048758 · NIAID · MICHIGAN STATE UNIVERSITY · PI MEEK, KATHERYN D · 2000 to 2016
$5.2M
Cancer Research UKCIHR MOP13639NIAID NIH HHS AI048758NIAID NIH HHS R01 AI048758
6 · The paper itself

Abstract

The protein kinase activity of the DNA-PKcs (DNA-dependent protein kinase catalytic subunit) and its autophosphorylation are critical for DBS (DNA double-strand break) repair via NHEJ (non-homologous end-joining). Recent studies have shown that depletion or inactivation of DNA-PKcs kinase activity also results in mitotic defects. DNA-PKcs is autophosphorylated on Ser2056, Thr2647 and Thr2609 in mitosis and phosphorylated DNA-PKcs localize to centrosomes, mitotic spindles and the midbody. DNA-PKcs also interacts with PP6 (protein phosphatase 6), and PP6 has been shown to dephosphorylate Aurora A kinase in mitosis. Here we report that DNA-PKcs is phosphorylated on Ser3205 and Thr3950 in mitosis. Phosphorylation of Thr3950 is DNA-PK-dependent, whereas phosphorylation of Ser3205 requires PLK1 (polo-like kinase 1). Moreover, PLK1 phosphorylates DNA-PKcs on Ser3205 in vitro and interacts with DNA-PKcs in mitosis. In addition, PP6 dephosphorylates DNA-PKcs at Ser3205 in mitosis and after IR (ionizing radiation). DNA-PKcs also phosphorylates Chk2 on Thr68 in mitosis and both phosphorylation of Chk2 and autophosphorylation of DNA-PKcs in mitosis occur in the apparent absence of Ku and DNA damage. Our findings provide mechanistic insight into the roles of DNA-PKcs and PP6 in mitosis and suggest that DNA-PKcs' role in mitosis may be mechanistically distinct from its well-established role in NHEJ.

Indexed as

Cell Cycle ProteinsCheckpoint Kinase 2DNA-Activated Protein KinaseHeLa CellsHumansMitosisNuclear ProteinsPhosphoprotein PhosphatasesPhosphorylationPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsCell Cycle ProteinsCheckpoint Kinase 2CHEK2 protein, humanDNA-Activated Protein KinaseNuclear ProteinsPhosphoprotein PhosphatasesPolo-Like Kinase 1PRKDC protein, humanprotein phosphatase 6Protein Serine-Threonine KinasesProto-Oncogene Proteins

Identifiers

PMID24844881
PMCPMC4069685
OpenAlexW2152595005

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.