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Study dataset

αKG-mediated carnitine synthesis drives DNA repair via histone acetylation

CRISPR screen, RNA-seq and histone proteomics in FT282 and Ovcar8 cell lines.

Listed Oct 6, 2026

  • Transcriptomic
  • Proteomic
  • Preclinical models
  • Ovarian

Overview

The Study

CCNE1-high ovarian cancers are proficient in homologous recombination and resist DNA-damaging therapies. This study asks which αKG-dependent enzymes they rely on:

  • CRISPR screen: 64 αKG-dependent dioxygenases under olaparib in FT282 and Ovcar8 cells
  • RNA-seq: Ovcar8 cells with CCNE1 overexpression and TMLHE knockdown (GEO GSE289735)
  • Histone proteomics: acetylation and methylation marks by condition (PRIDE PXD060690)

Key Findings

  • TMLHE: the first enzyme of carnitine synthesis is among the strongest dropouts in both cell lines.
  • Histone acetylation: αKG-driven carnitine synthesis feeds site-specific histone acetylation that promotes homologous recombination.
  • Therapeutic angle: blocking carnitine synthesis sensitizes CCNE1-high cells to olaparib, and L-carnitine reverses the effect.

In the Discovery Lab TRE

The paper's supplementary source data, the raw RNA-seq reads, and an independent DESeq2 reanalysis that agrees with the published fold changes (Pearson r = 0.882 over 12,346 genes for the first TMLHE hairpin).

Publications

Contributors

Investigators