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Bypass of blocking lesions by RNAPII reveals a novel stress induced by DNA damage [RNA-seq]

GSE261054 Homo sapiens (human) RNA-seq (gene expression) 62 samples Submitted 2026/02/10 Platform GPL34284Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 62 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
62 samples: 22 conditions, mostly in duplicateGroups 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
Bypass of blocking lesions by RNAPII reveals a novel stress induced by DNA damageGenes & development · 2026
Summary (written by the submitters)
Ultraviolet (UV) irradiation or platinum-based drugs generate bulky DNA lesions that impede transcription elongation by RNA Polymerase II (RNAPII). This unscheduled transcription elongation block triggers a stress response, which includes initiating transcription-coupled DNA repair, removing and degrading the halted RNAPII, and a global transcriptional shutdown.
Read the full summary ↓
However, the molecular and cellular consequences of RNAPII successfully bypassing these blocking lesions have remained unknown. Here, we have identified the acetyltransferase p300 as a regulator of the stress response when RNAPII stalls at blocking lesions. Indeed, p300 interacts with the halted RNAPII and controls its removal and degradation in a USP7-dependent mechanism. Notably, in p300-deficient cells, transcription persists despite DNA damage, as RNAPII bypasses blocking lesions, leading to mutant mRNAs and splicing variants accumulation. This persistent transcription activity is particularly detrimental post DNA damage as it results in toxic translation activity and higher DNA damage levels. These observations provide the first evidence that bypass of blocking lesions by RNAPII inhibits DNA repair as well as the cellular stress response. Our findings offer essential insights into the mechanisms of resistance to DNA damage and suggest strategies to enhance the efficacy of platinum-based drugs, such as cisplatin, in anti-tumor therapies.
Published in
Bypass of blocking lesions by RNAPII reveals a novel stress induced by DNA damage
Bañuelos CP, Caeiro LD, Cingaram PR et al. · Genes & development 2026 · PMID 41644268 · doi:10.1101/gad.353164.125
This dataset
Open GSE261054 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 GSE261054_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 PRJNA1084905 and SRA study SRP493756. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41644268) ↗
Study design
22 conditions, mostly in duplicate
Poly_Purif_p300KO_0J ×4 Poly_Purif_p300KO_20J_2h ×4 Poly_p300KO_0J ×2 Poly_p300KO_20J_2h ×2 Poly_p300KO_20J_3h ×2 Poly_Purif_p300KO_20J_3h ×2 Poly_Purif_WT_0J ×2 Poly_Purif_WT_20J_2h ×2 +28 more

Supports a between-group comparison across 48 samples.

How we read this: 22 replicated groups read from 62 sample titles; they account for 48 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

+ 22 more — browse all 62 samples with per-sample file links →

Datasets on a similar topic

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