Evidence map›Paper›PMID 37833256›Full record

ArticleNature communications2023

Transcriptional repression by a secondary DNA binding surface of DNA topoisomerase I safeguards against hypertranscription.

Mei Sheng Lau, Zhenhua Hu, Xiaodan Zhao, Yaw Sing Tan, Jinyue Liu, Hua Huang, Clarisse Jingyi Yeo, Hwei Fen Leong, Oleg V Grinchuk, Justin Kaixuan Chan and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. 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
1.1field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026
    Review
  3. Article
  4. 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

12 authors at 2 institutions in 2 countries.

Mei Sheng Lau *Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore. mslau@imcb.a-star.edu.sg.ORCID http://orcid.org/0000-0002-7867-9426
Zhenhua Hu *Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Xiaodan Zhao *Department of Physics, National University of Singapore, Singapore, 117551, Singapore.
Yaw Sing TanBioinformatics Institute (BII), A*STAR, 30 Biopolis Street, Matrix, Singapore, 138671, Singapore.ORCID http://orcid.org/0000-0002-2522-9421
Jinyue LiuGenome Institute of Singapore (GIS), A*STAR, 60 Biopolis Street, Genome, Singapore, 138672, Singapore.ORCID http://orcid.org/0000-0003-2094-6365
Hua HuangDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Clarisse Jingyi YeoInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Hwei Fen LeongInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Oleg V GrinchukInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Justin Kaixuan ChanInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.ORCID http://orcid.org/0009-0006-8670-4632
Jie YanDepartment of Physics, National University of Singapore, Singapore, 117551, Singapore. phyyj@nus.edu.sg.ORCID http://orcid.org/0000-0002-8555-7291
Wee-Wei TeeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore. wwtee@imcb.a-star.edu.sg.ORCID http://orcid.org/0000-0003-4952-6567
Agency for Science, Technology and Research · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regulation of global transcription output is important for normal development and disease, but little is known about the mechanisms involved. DNA topoisomerase I (TOP1) is an enzyme well-known for its role in relieving DNA supercoils for enabling transcription. Here, we report a non-enzymatic function of TOP1 that downregulates RNA synthesis. This function is dependent on specific DNA-interacting residues located on a conserved protein surface. A loss-of-function knock-in mutation on this surface, R548Q, is sufficient to cause hypertranscription and alter differentiation outcomes in mouse embryonic stem cells (mESCs). Hypertranscription in mESCs is accompanied by reduced TOP1 chromatin binding and change in genomic supercoiling. Notably, the mutation does not impact TOP1 enzymatic activity; rather, it diminishes TOP1-DNA binding and formation of compact protein-DNA structures. Thus, TOP1 exhibits opposing influences on transcription through distinct activities which are likely to be coordinated. This highlights TOP1 as a safeguard of appropriate total transcription levels in cells.

Indexed as

DNA Topoisomerases, Type ITranscription, GeneticAnimalsDNADNA ReplicationMiceMutationDNADNA Topoisomerases, Type I

Identifiers

PMID37833256
PMCPMC10576097
OpenAlexW4387608980

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.