Evidence map›Paper›PMID 37439356›Full record

ArticleNucleic acids research2023

TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair.

Ishita Ghosh, Youngho Kwon, Aida Badamchi Shabestari, Rupesh Chikhale, Jing Chen, Claudia Wiese, Patrick Sung, Arrigo De Benedetti

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.5field-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

18 citing papers in PubMed, 23 citations in OpenAlex.

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  12. iScience · 2024
    Article
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  16. Review
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  18. Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.International journal of molecular sciences · 2023
    Review
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 5 institutions in 2 countries.

Ishita GhoshDepartment of Biochemistry and Molecular Biology, Louisiana Health Science Center-Shreveport, Shreveport, Louisiana 71130, US2. Texas 78229, USA.
Youngho KwonDepartment of Biochemistry & Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Aida Badamchi ShabestariDepartment of Biochemistry & Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Rupesh ChikhaleDivision of Pharmacy & Optometry, University of Manchester, Manchester, UK.
Jing ChenDepartment of Molecular and Cellular Biochemistry and Proteomics Core, Center for Structural Biology, University of Kentucky, Lexington, KY, USA.
Claudia WieseDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
Patrick SungDepartment of Biochemistry & Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Arrigo De BenedettiDepartment of Biochemistry and Molecular Biology, Louisiana Health Science Center-Shreveport, Shreveport, Louisiana 71130, US2. Texas 78229, USA.ORCID 0000-0002-4198-8647
The University of Texas Health Science Center at San Antonio · USLouisiana State University Health Sciences Center Shreveport · USColorado State University · USUniversity of Kentucky · USUniversity of Manchester · GB

Funding

Mechanisms of DNA Homology-directed Genome Repair and Tumor SuppressionR35CA241801 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SUNG, PATRICK · 2019 to 2025
$6.0M
BRCA-dependent Mechanisms of Genome Maintenance and RepairR50CA265315 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI YOUNGHO KWON · 2022 to 2026
$818k
Define the role of NUCKS1 in homologous recombination DNA repair and cancer biologyR56ES021454 · NIEHS · COLORADO STATE UNIVERSITY · PI WIESE, CLAUDIA · 2019 to 2019
$225k
NCI NIH HHS R35 CA241801NCI NIH HHS R50 CA265315NIEHS NIH HHS R56 ES021454
6 · The paper itself

Abstract

Environmental agents like ionizing radiation (IR) and chemotherapeutic drugs can cause severe damage to the DNA, often in the form of double-strand breaks (DSBs). Remaining unrepaired, DSBs can lead to chromosomal rearrangements, and cell death. One major error-free pathway to repair DSBs is homologous recombination repair (HRR). Tousled-like kinase 1 (TLK1), a Ser/Thr kinase that regulates the DNA damage checkpoint, has been found to interact with RAD54, a central DNA translocase in HRR. To determine how TLK1 regulates RAD54, we inhibited or depleted TLK1 and tested how this impacts HRR in human cells using a ISce-I-GR-DsRed fused reporter endonuclease. Our results show that TLK1 phosphorylates RAD54 at three threonines (T41, T59 and T700), two of which are located within its N-terminal domain (NTD) and one is located within its C-terminal domain (CTD). Phosphorylation at both T41 and T59 supports HRR and protects cells from DNA DSB damage. In contrast, phosphorylation of T700 leads to impaired HRR and engenders no protection to cells from cytotoxicity and rather results in repair delay. Further, our work enlightens the effect of RAD54-T700 (RAD54-CTD) phosphorylation by TLK1 in mammalian system and reveals a new site of interaction with RAD51.

Indexed as

DNA RepairRecombinational DNA RepairAnimalsDNADNA DamageHomologous RecombinationHumansMammalsPhosphorylationProtein Serine-Threonine KinasesRad51 RecombinaseDNAProtein Serine-Threonine KinasesRad51 RecombinaseTLK1 protein, human

Identifiers

PMID37439356
PMCPMC10484734
OpenAlexW4384119515

What OpenQuestion holds

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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.