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Alpha-ketoglutarate -mediated carnitine synthesis promotes homologous recombination via histone acetylation

GSE289735 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/02/26 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
12 samples: 3 × Ovcar8 cells, control, vs 3 × Ovcar8 cells, CCNE1 overexpression, vs 3 × Ovcar8 cells, CCNE1 overexpression + shTMLHE #1, vs 3 × Ovcar8 cells, CCNE1 overexpression + shTMLHE #2,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
αKG-mediated carnitine synthesis drives DNA repair via histone acetylationNature · 2026
Summary (written by the submitters)
Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation.
Read the full summary ↓
αKG is required for the activity of αKG-dependent dioxygenases (αKGDDs), and prior work has shown that changes in αKGDD affect demethylases. Using a targeted CRISPR knockout library consisting of 64 αKGDDs, we discovered that Trimethyllysine Hydroxylase Epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for proliferation of HR-proficient cells in the presence of DNA damaging agents. Unexpectedly, αKG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation, while histone methylation was affected but dispensable. The increase in histone acetylation via αKG-dependent carnitine synthesis promoted HR-mediated DNA repair through site- and substrate-specific histone acetylation. These data demonstrate for the first time that HR-proficiency is mediated through αKG directly influencing histone acetylation via carnitine synthesis and provide a metabolic avenue to induce HR-deficiency and sensitivity to DNA damaging agents.
Published in
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation
Uboveja A, Yang B, Buj R et al. · Nature 2026 · PMID 42203879 · doi:10.1038/s41586-026-10584-7
This dataset
Open GSE289735 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE289735_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1224274 and SRA study SRP564184. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42203879) ↗
Study design
3 × Ovcar8 cells, control, vs 3 × Ovcar8 cells, CCNE1 overexpression, vs 3 × Ovcar8 cells, CCNE1 overexpression + shTMLHE #1, vs 3 × Ovcar8 cells, CCNE1 overexpression + shTMLHE #2,

Supports a case/control comparison: 9 samples read as cases, 3 as controls.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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