Evidence map›Paper›PMID 42056493›Full record

ArticleNature cell biology2026

ATM counteracts chromatin-bound cGAS during DNA replication.

Yunhao Song, Xiaojuan Ran, Yu Xu, Kartik Subramanian, Chao Dai, Mavrakis Konstantinos, Li Lan, Vipin Yadav, Lee Zou

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

9 authors.

Yunhao SongDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Xiaojuan RanDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Yu XuDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Kartik SubramanianMechanisms of Cancer Resistance Thematic Research Center, Bristol Myers Squibb, Boston, MA, USA.
Chao DaiMechanisms of Cancer Resistance Thematic Research Center, Bristol Myers Squibb, Boston, MA, USA.
Mavrakis KonstantinosMechanisms of Cancer Resistance Thematic Research Center, Bristol Myers Squibb, Boston, MA, USA.
Li LanDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0383-6172
Vipin YadavMechanisms of Cancer Resistance Thematic Research Center, Bristol Myers Squibb, Boston, MA, USA.
Lee ZouDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA. lee.zou@duke.edu.ORCID http://orcid.org/0000-0003-3094-1058

Funding

Understanding and targeting the DNA replication stress in cancer cellsR35CA263934 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Lee Zou · 2021 to 2026
$5.2M
Mechanisms of replication fork protection and recoveryR01CA248526 · NCI · WASHINGTON UNIVERSITY · PI Alessandro Vindigni, Lee Zou · 2020 to 2026
$3.6M
Leica Stellaris Confocal for a Campus-wide Shared ResourceS10OD034340 · OD · DUKE UNIVERSITY · PI CAMERON, LISA A. · 2024 to 2024
$686k
NCI NIH HHS R01 CA248526NCI NIH HHS R35 CA263934NIH HHS S10 OD034340
6 · The paper itself

Abstract

Cyclic GMP-AMP synthase (cGAS), a DNA sensor that activates type-I interferon responses, is restrained in the nucleus through chromatin binding, but its impact on DNA metabolism remains unknown. Here we show that chromatin-bound cGAS impedes DNA replication forks unless countered by ATM. Upon ATM loss, chromatin-bound cGAS slows replication forks, increases nascent DNA fragmentation and activates cytosolic cGAS. Remarkably, all these effects are alleviated upon the loss of cGAS chromatin binding, suggesting that ATM enables tolerance to chromatin-bound cGAS. Mechanistically, ATM, backed by ATR, releases cGAS from chromatin by phosphorylating MRE11. ATR inhibition in ATM-deficient cells exacerbates replication stress, causing synthetic lethality and stimulated interferon response. In ATM-deficient cancer cells, cGAS dictates replication stress and ATR inhibitor sensitivity, highlighting its potential as a biomarker for ATR-targeted therapy. Together, our findings uncover a regulatory circuit in which ATM and chromatin-bound cGAS jointly maintain the homeostasis of replication and cGAS signalling in cycling cells.

Indexed as

Ataxia Telangiectasia Mutated ProteinsChromatinCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA ReplicationGenomic InstabilityAnimalsCell Line, TumorGene Knockout TechniquesHumansMiceAtaxia Telangiectasia Mutated ProteinsATM protein, humanAtm protein, mouseATR protein, humanAtr protein, mousecGAS protein, humancGAS protein, mouseChromatinCyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase

Identifiers

PMID42056493
PMCPMC13334574

What OpenQuestion holds

Textmetadata
LicenceTDM
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.