Evidence map›Paper›PMID 41022786›Full record

ArticleNature communications2025

RNA polymerase II is a polar roadblock to a progressing DNA fork.

Taryn M Kay, James T Inman, Lucyna Lubkowska, Tung T Le, Jin Qian, Porter M Hall, Sahil Batra, Dirk Remus, Dong Wang, Mikhail Kashlev and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Taryn M KayBiophysics Program, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0003-3622-2281
James T InmanDepartment of Physics & LASSP, Cornell University, Ithaca, NY, USA.
Lucyna LubkowskaRNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Tung T LeDepartment of Physics & LASSP, Cornell University, Ithaca, NY, USA.
Jin QianDepartment of Physics & LASSP, Cornell University, Ithaca, NY, USA.
Porter M HallDepartment of Physics & LASSP, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-5403-719X
Sahil BatraMolecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-4210-3991
Dirk RemusMolecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5155-181X
Dong WangDivision of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-2829-1546
Mikhail KashlevRNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.ORCID http://orcid.org/0000-0002-1260-6486
Michelle D WangDepartment of Physics & LASSP, Cornell University, Ithaca, NY, USA. mwang@physics.cornell.edu.ORCID http://orcid.org/0000-0001-9137-3790

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
TRAINING IN MOLECULAR PHYSICS OF BIOLOGICAL SYSTEMST32GM008267 · NIGMS · CORNELL UNIVERSITY ITHACA · PI WANG, MICHELLE D. · 1988 to 2021
$9.6M
Molecular Mechanisms for DNA Damage Processing by Transcription MachineryR01GM102362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, DONG · 2013 to 2025
$5.6M
Molecular mechanism of eukaryotic chromosome replicationR35GM152094 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Dirk Remus · 2024 to 2026
$2.0M
Fundamental Biological Processes Under TorsionR01GM136894 · NIGMS · CORNELL UNIVERSITY · PI WANG, MICHELLE D. · 2020 to 2023
$1.2M
NCI NIH HHS P30 CA008748NIGMS NIH HHS R01 GM102362NIGMS NIH HHS R01 GM136894NIGMS NIH HHS R35 GM152094NIGMS NIH HHS T32 GM008267U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM102362U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM136894U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM008267
6 · The paper itself

Abstract

Transcription-replication conflicts threaten genome stability. Although head-on conflicts are more detrimental and prone to R-loop formation than co-directional conflicts, the cause of this RNA polymerase roadblock polarity remains unclear, and proposed structures of these R-loops are speculative. Here, we examine the Pol II roadblock to a DNA fork advanced by mechanical unzipping to mimic replisome progression. We found that a head-on Pol II with a minimal transcript resists disruption more strongly, revealing inherent polarity. Moreover, an elongating Pol II with a long RNA transcript becomes an even more potent roadblock, mediated by RNA-DNA hybrid formation. Surprisingly, when a Pol II collides with the DNA fork head-on and becomes backtracked, a hybrid can form in front of Pol II, creating a topological lock that traps Pol II at the fork. Our findings capture the basal properties of Pol II interactions with a DNA fork, revealing significant implications for transcription-replication conflicts.

Indexed as

DNADNA ReplicationRNA Polymerase IIR-Loop StructuresRNATranscription, GeneticDNARNARNA Polymerase II

Identifiers

PMID41022786
PMCPMC12479915

What OpenQuestion holds

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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.