GEO series

NSUN2 Facilitates Dicer Cleavage of DNA Damage-Associated R-Loops to Promote Repair [ChIP-Seq]

GSE294470 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2025/08/27 Platform GPL34284

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 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: 12 samples: 3 × U2OS cells +4OHT vs 3 × U2OS cellsGroups 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: NSUN2 facilitates DICER cleavage of DNA damage-associated R-loops to promote repairNature communications · 2025

Summary (written by the submitters)

DNA integrity is constantly challenged by both endogenous and exogenous damaging agents, resulting in various forms of damage. Failure to repair DNA accurately leads to genomic instability, a hallmark of cancer. Distinct pathways exist to repair different types of DNA damage. Double-strand breaks (DSBs) represent particularly severe form of damage, due to physical separation of DNA strands.

Read the full summary ↓

Repair of DSBs requires activity of RNA Polymerase II (RNAPII) and generation of Damage-associated transcripts (DARTs). Here we show that the RNA m5C-methyltransferase NSUN2 localizes to DSBs in transcription-dependent manner, where it binds to and methylates DARTs. Depletion of NSUN2 results in an accumulation of nascent DARTs around DSBs, specifically of the de novo primary DARTs. Furthermore, we detected an RNA-dependent interaction between NSUN2 and DICER, which was stimulated by DNA damage. NSUN2 activity promoted Dicer cleavage of DARTs associated R-loops, which is required for efficient DNA repair. We report a previously unrecognized role of the RNA m5C-methyltransferase NSUN2 within RNA-dependent DNA damage response, highlighting its function as a DICER chaperone for the clearance of non-canonical substrates such as DARTs, thereby contributing to genomic integrity.

Published in

NSUN2 facilitates DICER cleavage of DNA damage-associated R-loops to promote repair

Alagia A, Ajit K, Di Fazio A et al. · Nature communications 2025 · PMID 40849328 · doi:10.1038/s41467-025-63220-9

This dataset

Open GSE294470 in finder → Find more human ChIP / ATAC / CUT&Tag 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 GSE294470_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 PRJNA1249507 and SRA study SRP577843. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40849328) ↗

Study design

3 × U2OS cells +4OHT vs 3 × U2OS cells

Supports a between-group comparison across 6 samples.

How we read this: 2 replicated groups read from 12 sample titles; they account for 6 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

GSM8907661 U2OS cells +4OHT rep1 U2OS cells +4OHT
GSM8907662 U2OS cells +4OHT rep2 U2OS cells +4OHT
GSM8907663 U2OS cells +4OHT rep3 U2OS cells +4OHT
GSM8907664 U2OS cells rep1 U2OS cells
GSM8907665 U2OS cells rep2 U2OS cells
GSM8907666 U2OS cells rep3 U2OS cells
GSM8907667 U2OS cells +4OHT rep1 (Input)
GSM8907668 U2OS cells +4OHT rep2 (Input)
GSM8907669 U2OS cells +4OHT rep3 (Input)
GSM8907670 U2OS cells rep1 (Input)
GSM8907671 U2OS cells rep2 (Input)
GSM8907672 U2OS cells rep3 (Input)

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