Evidence map›Paper›PMID 41720076›Full record

ArticleMolecular cell2026

Large-scale mapping of environmental-genetic interactions illustrates the dynamic nature of cell-cycle and DNA repair regulation.

Benjamin W Herken, Garrett T Wong, Anna Mäkiniemi, Emma Lundberg, Thomas M Norman, Luke A Gilbert

Abstract read
In one paragraph

Article in Molecular cell, 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. 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

6 authors.

Benjamin W HerkenTetrad Graduate Program, University of California, San Francisco, San Francisco 94518, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco 94518, USA; Arc Institute, Palo Alto, CA 94305, USA.
Garrett T WongHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco 94518, USA; Arc Institute, Palo Alto, CA 94305, USA; Biological and Medical Informatics Graduate Program, University of California, San Francisco 94518, USA.
Anna MäkiniemiScience for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology, Stockholm, Sweden.
Emma LundbergScience for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology, Stockholm, Sweden; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Thomas M NormanMemorial Sloan Kettering Cancer Center, New York 10065, USA.
Luke A GilbertHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco 94518, USA; Arc Institute, Palo Alto, CA 94305, USA; Department of Urology, University of California, San Francisco 94518, USA. Electronic address: luke@arcinstitute.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
PROMINENT - UCSFOT2CA278665 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ALLAN BALMAIN · 2022 to 2026
$8.9M
Predictive engineering of cellular transcriptional stateDP2GM140925 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI NORMAN, THOMAS MAXWELL · 2020 to 2020
$2.7M
A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
NCI NIH HHS DP2 CA239597NCI NIH HHS OT2 CA278665NCI NIH HHS P30 CA008748NIGMS NIH HHS DP2 GM140925
6 · The paper itself

Abstract

Cells integrate exogenous and endogenous signals to grow, repair, or die. This is likely achieved through dynamic functional associations between genes, but measuring these relationships at scale is non-trivial. Here, we evaluate genetic associations in response to cell-cycle interruption, genotoxic perturbation, and nutrient deprivation using conditional genetic interaction (GI) mapping in human cells. In five maps measuring ∼250,000 GIs or higher-order environmental interactions, we discover widespread rewiring of relationships between genes, complexes, and ontologies across conditions. Specific bioprocesses drive the rewiring signal in each environmental state, as highlighted in our findings that the TIP60 and PP2A complexes radically alter their interaction profiles after inhibition of ATR. This resource reveals numerous genetic relationships for the fields of DNA damage signaling, DNA repair, and cell-cycle control and explores their context specificity. Our work advances a framework for using GI maps to explore environmental rewiring.

Indexed as

Cell CycleDNA RepairGene-Environment InteractionAtaxia Telangiectasia Mutated ProteinsDNA DamageGene Regulatory NetworksHumansProtein Phosphatase 2Signal TransductionAtaxia Telangiectasia Mutated ProteinsATR protein, humanProtein Phosphatase 2ATRcell cycleCRISPRiDNA repairgenetic interactionmetabolismrewiring

Identifiers

PMID41720076
PMCPMC13068139

What Socratic 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 Socratic graph.