Evidence map›Paper›PMID 39395804›Full record

ArticleThe Journal of biological chemistry2024

CDK-dependent phosphorylation regulates PNKP function in DNA replication.

Fatemeh Mashayekhi, Elham Zeinali, Cassandra Ganje, Mesfin Fanta, Lei Li, Roseline Godbout, Michael Weinfeld, Ismail Hassan Ismail

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Fatemeh MashayekhiDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Elham ZeinaliDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Cassandra GanjeDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Mesfin FantaDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Lei LiDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Roseline GodboutDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Michael WeinfeldDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: mweinfel@ualberta.ca.
Ismail Hassan IsmailDepartment of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt. Electronic address: iismail@ualberta.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Okazaki fragment maturation (OFM) stands as a pivotal DNA metabolic process, crucial for genome integrity and cell viability. Dysregulation of OFM leads to DNA single-strand breaks-accumulation, which is linked to various human diseases such as cancer and neurodegenerative disorders. Recent studies have implicated LIG3-XRCC1 acting in an alternative OFM pathway to the canonical FEN1-LIG1 pathway. Here, we reveal that polynucleotide kinase-phosphatase (PNKP) is another key participant in DNA replication, akin to LIG3-XRCC1. Through functional experiments, we demonstrate PNKP's enrichment at DNA replication forks and its association with PCNA, indicating its involvement in DNA replication processes. Cellular depletion of PNKP mirrors defects observed in OFM-related proteins, highlighting its significance in replication fork dynamics. Additionally, we identify PNKP as a substrate for cyclin-dependent kinase 1 and 2 (CDK1/2), which phosphorylates PNKP at multiple residues. Mutation analysis of these phosphorylation sites underscores the importance of CDK-mediated PNKP phosphorylation in DNA replication. Our findings collectively indicate a novel role for PNKP in facilitating Okazaki fragments joining, thus shedding light on its contribution to genome stability maintenance.

Indexed as

DNA ReplicationPhosphotransferases (Alcohol Group Acceptor)CDC2 Protein KinaseCyclin-Dependent Kinase 2DNADNA Repair EnzymesHumansPhosphorylationProliferating Cell Nuclear AntigenCDC2 Protein KinaseCDK2 protein, humanCyclin-Dependent Kinase 2DNADNA Repair EnzymesOkazaki fragmentsPCNA protein, humanPhosphotransferases (Alcohol Group Acceptor)PNKP protein, humanProliferating Cell Nuclear AntigenCDKsDNA replicationFEN1genome instabilityOkazaki fragmentsPNKP

Identifiers

PMID39395804
PMCPMC11650725

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.