Evidence map›Paper›PMID 41408469›Full record

ArticleCell death and differentiation2026

cGAS restricts PARP1-mediated microhomology-mediated end joining by suppressing poly-ADP-ribosylation.

Haibo Yang, Boya Gao, Bo Wu, Wenjing Li, Xueping Zhu, Laiyee Phoon, Jing Luo, Fu Gui, Weixing Zhao, Li Jia and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2026. 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. 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

11 authors.

Haibo YangDepartment of Urology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA.
Boya GaoDepartments of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.
Bo WuDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Wenjing LiDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Xueping ZhuCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Laiyee PhoonDepartments of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA.
Jing LuoDepartment of Urology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1523-4665
Fu GuiDepartment of Urology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8329-7118
Weixing ZhaoDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-5746-3696
Li JiaDepartment of Urology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA. ljia@bwh.harvard.edu.ORCID http://orcid.org/0000-0003-4017-1157
Li LanDepartments of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA. li.lan@duke.edu.

Funding

Androgen receptor pathway inhibition through targeting PARP-2 in castration-resistant prostate cancerR01CA262524 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI JIA, LI · 2021 to 2025
$2.0M
MMS22L loss and PARP inhibition in prostate cancerR01CA279410 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Li Jia · 2023 to 2026
$1.6M
Understanding and Targeting the R-Loop-Mediated DNA Damage Response at TelomeresR01CA282939 · NCI · DUKE UNIVERSITY · PI Li Lan · 2023 to 2026
$1.5M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01CA262524Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01CA279410Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01CA282939NCI NIH HHS R01 CA262524NCI NIH HHS R01 CA279410NCI NIH HHS R01 CA282939U.S. Department of Defense (United States Department of Defense) W81XWH-22-1-0477
6 · The paper itself

Abstract

Repair of DNA double-strand breaks (DSBs) is essential for cells to maintain genome stability and cell survival. While cyclic GMP-AMP synthase (cGAS) is best known for its role in innate immunity, emerging evidence reveals that it plays regulatory roles in DNA damage response. In this study, we demonstrate that cGAS suppresses PARP1-mediated poly(ADP-ribose) (PAR) formation at both double-stranded DNA (dsDNA) and DNA:RNA hybrids. As a result, cGAS deficiency enhances PARP1-mediated microhomology-mediated end joining (MMEJ). Since MMEJ competes with transcription-coupled homologous recombination (TC-HR) at actively transcribed genomic regions, cGAS-mediated suppression of MMEJ consequently leads to efficient TC-HR with increased recruitment of RAD52 and RAD51. Mechanistically, the zinc finger domain of cGAS binds PAR, inhibiting PARP1 activation. In prostate cancer cells, loss of cGAS increases dependency on PARP1, rendering them more sensitive to PARP inhibitors. Collectively, our findings uncover a noncanonical role for cGAS in negatively regulating PARP1-mediated MMEJ and suggest its potential as a therapeutic biomarker in prostate cancer.

Indexed as

Cyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA End-Joining RepairPoly (ADP-Ribose) Polymerase-1Poly ADP RibosylationDNA Breaks, Double-StrandedHumansPoly Adenosine Diphosphate RibosecGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthasePARP1 protein, humanPoly Adenosine Diphosphate RibosePoly (ADP-Ribose) Polymerase-1

Identifiers

PMID41408469
PMCPMC13246745

What OpenQuestion holds

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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.