Evidence map›Paper›PMID 40146629›Full record

ArticleeLife2025

CDK-mediated phosphorylation of PNKP is required for end-processing of single-strand DNA gaps on Okazaki fragments and genome stability.

Kaima Tsukada, Rikiya Imamura, Tomoko Miyake, Kotaro Saikawa, Mizuki Saito, Naoya Kase, Lingyan Fu, Masamichi Ishiai, Yoshihisa Matsumoto, Mikio Shimada

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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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

10 authors.

Kaima Tsukada *Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-6725-9514
Rikiya Imamura *Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Tomoko MiyakeLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-3389-4007
Kotaro SaikawaLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Mizuki SaitoLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Naoya KaseLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Lingyan FuLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Masamichi IshiaiNational Cancer Center Research Institute, Tokyo, Japan.ORCID https://orcid.org/0000-0003-4313-9945
Yoshihisa MatsumotoLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-0758-290X
Mikio ShimadaLaboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-1980-9187

Funding

Japan Society for the Promotion of Science JP15H02817Japan Society for the Promotion of Science JP17K20042Japan Society for the Promotion of Science JP18K11642Japan Society for the Promotion of Science JP20H04334Japan Society for the Promotion of Science JP20J13601Japan Society for the Promotion of Science JP22K12369
6 · The paper itself

Abstract

Polynucleotide kinase phosphatase (PNKP) has enzymatic activities as 3'-phosphatase and 5'-kinase of DNA ends to promote DNA ligation and repair. Here, we show that cyclin-dependent kinases (CDKs) regulate the phosphorylation of threonine 118 (T118) in PNKP. This phosphorylation allows recruitment to the gapped DNA structure found in single-strand DNA (ssDNA) nicks and/or gaps between Okazaki fragments (OFs) during DNA replication. T118A (alanine)-substituted PNKP-expressing cells exhibited an accumulation of ssDNA gaps in S phase and accelerated replication fork progression. Furthermore, PNKP is involved in poly (ADP-ribose) polymerase 1 (PARP1)-dependent replication gap filling as part of a backup pathway in the absence of OFs ligation. Altogether, our data suggest that CDK-mediated PNKP phosphorylation at T118 is important for its recruitment to ssDNA gaps to proceed with OFs ligation and its backup repairs via the gap-filling pathway to maintain genome stability.

Indexed as

Cyclin-Dependent KinasesDNADNA, Single-StrandedGenomic InstabilityPhosphotransferases (Alcohol Group Acceptor)DNA RepairDNA Repair EnzymesDNA ReplicationHumansPhosphorylationCyclin-Dependent KinasesDNADNA Repair EnzymesDNA, Single-StrandedOkazaki fragmentsPhosphotransferases (Alcohol Group Acceptor)PNKP protein, humancell biologyDNA repairDNA replicationhumanOkazaki fragmentPNKP

Identifiers

PMID40146629
PMCPMC11949490

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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.