Evidence map›Paper›PMID 34117057›Full record

ArticleScience advances2021

Polθ reverse transcribes RNA and promotes RNA-templated DNA repair.

Gurushankar Chandramouly, Jiemin Zhao, Shane McDevitt, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Taylor Treddinick, Felicia Wednesday Lopezcolorado, Tatiana Kent, Labiba A Siddique and 8 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.3field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
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  14. Disruption of Microhomology-mediated End-joining in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025
    Article
  15. De novo rates of aProceedings of the National Academy of Sciences of the United States of America · 2025
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  20. Advancing Precision Medicine: Recent Innovations in Gene Editing Technologies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review

6 more citing papers are in PubMed but not listed here.

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

18 authors at 4 institutions in 1 country.

Gurushankar ChandramoulyDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0002-4258-9859
Jiemin ZhaoMolecular and Computational Biology, USC Dornsife Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-8939-2156
Shane McDevittDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-9360-2841
Timur RusanovDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0002-4054-3611
Trung HoangDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Nikita BorisonnikDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Taylor TreddinickDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0002-0106-5194
Felicia Wednesday LopezcoloradoBeckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID 0000-0002-2916-6042
Tatiana KentDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-8237-0184
Labiba A SiddiqueDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0003-3446-3946
Joseph MallonDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Jacklyn HuhnDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-7503-3040
Zainab ShodaDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0003-1657-5725
Ekaterina KashkinaDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Alessandra BrambatiDepartment of Cell Biology, New York University School of Medicine, New York, NY, USA.ORCID 0000-0002-3816-425X
Jeremy M StarkBeckman Research Institute of the City of Hope, Duarte, CA, USA.
Xiaojiang S ChenMolecular and Computational Biology, USC Dornsife Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0001-9574-0551
Richard T PomerantzDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. richard.pomerantz@jefferson.edu.ORCID 0000-0003-1194-9871
Thomas Jefferson University · USCity of Hope · USUniversity of Southern California · USNew York University · US

Funding

The role of O-GlcNAcylation in DNA damage repair and cancer therapyR01CA240392 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI STARK, JEREMY MICHAEL · 2019 to 2023
$2.0M
Regulation of Single Strand Annealing Repair of Mammalian Chromosomal BreaksR01CA197506 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI STARK, JEREMY MICHAEL · 2016 to 2020
$1.9M
Structure and Function of DNA Polymerase ThetaR01GM130889 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2019 to 2022
$1.6M
Mechanisms of RNA-DNA repairR01GM137124 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2020 to 2023
$1.5M
NCI NIH HHS R01 CA197506NCI NIH HHS R01 CA240392NIGMS NIH HHS R01 GM130889NIGMS NIH HHS R01 GM137124
6 · The paper itself

Abstract

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2'-hydroxyl groups like retroviral RTs. Last, we find that Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.

Indexed as

DNA-Directed DNA PolymeraseRNAAnimalsDeoxyribonucleotidesDNADNA RepairHumansMammalsRibonucleotidesDeoxyribonucleotidesDNADNA-Directed DNA PolymeraseRibonucleotidesRNA

Identifiers

PMID34117057
PMCPMC8195485
OpenAlexW3168097770

What OpenQuestion holds

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LicenceCC BY-NC
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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.