Recurrent reversible mutations at gaf1 driving metastable TORC1 inhibitor resistance in fission yeast.

Dan L, Ye X, Liu S, Zhang J, Qiang Z, Yang X, Li W · 2026 · Microbiology Spectrum · Atlas ID DAN2026

What this study shows

Metastable resistance to TORC1 inhibitors (rapamycin plus caffeine) in fission yeast is driven by recurrent, spontaneously reversible loss-of-function mutations in gaf1, a GATA transcription factor and negative growth regulator downstream of TORC1 - a genetic (not epigenetic) toggle that can silently contaminate lab yeast stocks.

Abstract

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Metastable phenotypic inheritance is often attributed to epigenetic mechanisms, but reversible genetic alterations can produce similar instability. Here, we investigated the basis of unstable resistance to TORC1 inhibitor (rapamycin plus caffeine) in fission yeast. Six independent, metastable resistant mutants were isolated. Genetic mapping positioned the causal lesion to a single Mendelian locus, identified as gaf1, encoding a GATA transcription factor and a key negative regulator of growth downstream of TORC1.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Fission yeast (Schizosaccharomyces pombe)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Fission yeast (Schizosaccharomyces pombe)
Journal	Microbiology Spectrum
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1128/spectrum.01467-26 · PMID 42752201

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	rapamycin plus caffeine selection; gaf1 loss-of-function and wild-type allele restoration
Target	TORC1 signalling output via the GATA transcription factor Gaf1
Model	fission yeast (Schizosaccharomyces pombe)
Effect	Reversible loss-of-function mutations in gaf1 were necessary and sufficient for metastable resistance to TORC1 inhibition, with derepression of translation and metabolic programmes on drug treatment.

In the Atlas

Cite this paper

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Dan, L., Ye, X., Liu, S., Zhang, J., Qiang, Z., Yang, X., & Li, W. (2026). Recurrent reversible mutations at gaf1 driving metastable TORC1 inhibitor resistance in fission yeast. Microbiology Spectrum. https://doi.org/10.1128/spectrum.01467-26

@article{DAN2026,
  author       = {Dan, L. and Ye, X. and Liu, S. and Zhang, J. and Qiang, Z. and Yang, X. and Li, W.},
  title        = {{Recurrent reversible mutations at gaf1 driving metastable TORC1 inhibitor resistance in fission yeast}},
  journal      = {Microbiology Spectrum},
  year         = {2026},
  doi          = {10.1128/spectrum.01467-26},
  note         = {PMID: 42752201},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record DAN2026) [Data set]. https://mtor-atlas.org/study/DAN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_DAN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record DAN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/DAN2026/},
  doi          = {10.5281/zenodo.22059963}
}

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