← BioTransfer GEO Dataset Finder
GEO series

Mechanism for local attenuation of DNA replication at double-strand breaks

GSE254206 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 97 samples Submitted 2025/02/19 Platform GPL24676Platform GPL21290Platform GPL20301Platform GPL30173
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 97 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
97 samples: 47 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.
Summary (written by the submitters)
DNA double-strand breaks (DSBs) destroy the continuity of our genome with consequences for malignant transformation. Massive DNA damage can elicit a cellular checkpoint response that prevents cell proliferation. However, how highly aggressive cancer cells, which can tolerate widespread DNA damage, respond to DSBs alongside continuous chromosome duplication is unknown.
Read the full summary ↓
Here we show that DSBs induce a local, hitherto unreported genome maintenance mechanism that inhibits replication initiation in DSB-containing topologically associating domains (TADs) without affecting DNA synthesis at other genomic locations. This process is facilitated by Mediators of Replication and DSBs (MRDs). In normal and cancer cells, MRDs include the TIMELESS-TIPIN complex and the WEE1 kinase, which actively dislodges the TIMELESS-TIPIN complex from replication origins adjacent to DSBs and prevents initiation of DNA synthesis at DSB-containing TADs. Dysregulation of MRDs, or disruption of 3D chromatin architecture by dissolving TADs, results in inadvertent replication in damaged chromatin and increased DNA damage in cancer cells. We propose that the intact MRD cascade precedes DSB repair to prevent genomic instability, which is otherwise observed when replication is forced, or when genome architecture is challenged, in the presence of DSBs. These observations reveal a previously undiscovered vulnerability in the DNA replication machinery that may be exploited to therapeutically target cancer cells.
This dataset
Open GSE254206 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 GSE254206_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 PRJNA1069015 and SRA study SRP485918. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
47 conditions, mostly in duplicate
AsiSI_U2OS_4OHT_BrdU_seq_Figure1c_EDF3d ×2 AsiSI_U2OS_4OHT_MCM2pS139_ChIP_EDF8b_Seq ×2 AsiSI_U2OS_4OHT_MCM4_ChIP_EDF8b_Seq ×2 AsiSI_U2OS_4OHT_NS_Seq_Figure3abc_EDF8a ×2 AsiSI_U2OS_4OHT_pSIRT1_ChIP_EDF8b_Seq ×2 AsiSI_U2OS_4OHT_TIMELESS_ChIP_seq_Figure3ab_E… ×2 AsiSI_U2OS_4OHT_TIPIN_ChIP_seq_Figure3ab_EDF8a ×2 AsiSI_U2OS_4OHT_yH2AX_ChIP_seq_Figure1c3a_EDF… ×2 +42 more

Supports a between-group comparison across 94 samples.

How we read this: 47 replicated groups read from 97 sample titles; they account for 94 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

+ 57 more — browse all 97 samples with per-sample file links →

Datasets on a similar topic

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.