Article

Ultramutagenesis through combined Msh2 depletion and proofreading-deficient DNA polymerase ε expression enhances small molecule target identification in forward genetic screens

2026-06-29

Abstract excerpt

<h4>ABSTRACT</h4> DNA mismatch repair (MMR) deficiency has been widely utilized in forward genetic screens to identify drug resistance mutations and elucidate the mechanisms of action of cytotoxic small molecules. However, MMR deficiency generates a characteristic mutational signature enriched for C>T transitions that precludes saturation of mutagenesis. We hypothesized that expression of proofreading deficient D...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 4ed54954-9051-5845-936c-965ebd41b8a1
DOI: 10.64898/2026.06.26.734921

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Ultramutagenesis through combined Msh2 depletion and proofreading-deficient DNA polymerase ε expression enhances small molecule target identification in forward genetic screensDOI 10.64898/2026.06.26.734921Read

Anticipating on-target resistance to WRN inhibitors in microsatellite unstable cancersSemantic proximity Read

Unveiling Replication Timing-Dependent Mutational Biases: Mechanistic Insights from Gene Knockouts and Genotoxins Exposures.Semantic proximity Read

A p53-dependent FBXO44-RAD18 axis limits mutagenesis by terminating translesion DNA synthesisSemantic proximity Read

AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer.Semantic proximity Read

Mismatch repair dissection by in vivo RNAi reveals dose-dependent modulators of somatic instability and proteome remodeling in Huntington’s diseaseSemantic proximity Read

On-target mutations confer resistance to WRN helicase inhibitors in Microsatellite Unstable Cancer CellsSemantic proximity Read

Deficiency in POLE exonuclease causes synthetic lethality in highly aneuploid cancer cellsSemantic proximity Read

p53 suppresses mutagenic RAD52 and POLθ pathways by orchestrating DNA replication restart homeostasisSemantic proximity Read

Cytidine deaminase protects pancreatic cancer cells from replicative stress and drives resistance to DNA-targeting drugsSemantic proximity Read

PI3K/mTOR activity sensitizes cancer cells to nucleolar stressSemantic proximity Read

Multimodal interrogation establishes the AAA+ ATPase RUVBL1 as a prognostic driver and tractable dependency in malignant pleural mesotheliomaSemantic proximity Read

Replication DNA polymerases, genome instability and cancer therapiesSemantic proximity Read