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YTHDC1 cooperates with the THO complex to prevent RNA damage-induced DNA breaks

GSE283317 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 30 samples Submitted 2024/12/03 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 30 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
30 samples: 14 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
YTHDC1 cooperates with the THO complex to prevent RNA-damage-induced DNA breaksMolecular cell · 2025
Summary (written by the submitters)
Certain environmental toxins are nucleic acid damaging agents, as are many chemotherapeutics used for cancer therapy. These agents induce various adducts in DNA as well as RNA. Indeed, most of the nucleic acid adducts (>90%) formed due to these chemicals, such as alkylating agents, occur in RNA. However, compared to the well-studied mechanisms for DNA alkylation repair, the biological consequences of RNA damage are largely unexplored.
Read the full summary ↓
Here, we demonstrate that RNA damage can directly result in loss of genome integrity. Specifically, we show that a human YTH domain-containing protein, YTHDC1, regulates alkylation damage responses in association with the THO complex (THOC). In addition to its established binding to N6-methyladenosine (m6A)-containing RNAs, YTHDC1 binds to N1-methyladenosine (m1A)-containing RNAs upon alkylation. In the absence of YTHDC1, alkylation damage results in increased alkylation damage sensitivity and DNA breaks. Such phenotypes are fully attributable to RNA damage, since an RNA-specific dealkylase can rescue these phenotypes. These RNA damage-induced DNA breaks (RDIBs) depend on R-loop formation and the processing is mediated by the factors involved in the transcription-coupled nucleotide excision repair. Strikingly, in the absence of YTHDC1 or THOC, an RNA m1A methyltransferase targeted to the nucleus is sufficient to induce DNA breaks. Our results uncover a unique role of YTHDC1-THOC in base damage responses by preventing RDIBs, providing definitive evidence for how damaged RNAs can impact genomic integrity.
Published in
YTHDC1 cooperates with the THO complex to prevent RNA-damage-induced DNA breaks
Tsao N, Lombardi PM, Park A et al. · Molecular cell 2025 · PMID 40037355 · doi:10.1016/j.molcel.2025.02.003
This dataset
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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 GSE283317_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1193090 and SRA study SRP548783. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40037355) ↗
Study design
14 conditions, mostly in duplicate
HeLa, non-treated, YTHDC1 CLIP, ×2 HeLa, MMS-treated, YTHDC1 CLIP, ×2 HeLa, MMS-treated, Input, control, ×2 HeLa, MMS-treated, Input, YTHDC1 KD, ×2 HeLa, MMS-treated, IP, control, ×2 HeLa, MMS-treated, IP, YTHDC1 KD, ×2 HeLa, non-treated, Mnase-IP, control, ×2 HeLa, non-treated, dRNH-IP, control, ×2 +8 more

Supports a between-group comparison across 28 samples.

How we read this: 14 replicated groups read from 30 sample titles; they account for 28 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
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