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TOP2B cooperates with ATRX to resolve G-quadruplexes and maintain replication fork stability in glioma

GSE275821 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/11/13 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
12 samples: 12 conditions, mostly in triplicateGroups 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
ATRX cooperates with TOP2B for replication fork stability and DNA damage response through G-quadruplex regulationNucleic acids research · 2025
Summary (written by the submitters)
ATRX is a chromatin remodeling protein that maintains genomic stability by resolving G-quadruplex (G4) DNA structure. However, the details of resolving G4 by ATRX remain unclear. Here, we unveil that TOP2B and ATRX collaborate to maintain genomic stability by regulating G4. ATRX deficiency causes the accumulation of G4 and increases cells’ reliance on TOP2B to resolve G4 structures and maintain replication fork stability.
Read the full summary ↓
CX-5461, as a TOP2B poison, stabilizes G4 by trapping TOP2B on DNA as well as inhibiting the formation of the ATRX-TOP2B complex and its recruitment to G4 sites. CX-5461 treatment resulted in the entrapment of TOP2B and the subsequent hyperaccumulation of G4 in ATRX-deficient glioma cells, ultimately leading to genomic instability and cell death. Furthermore, we found that YTHDF3 promotes ATRX protein synthesis through m6A modification. Our findings suggest that targeting TOP2B with CX-5461 has therapeutic potential for ATRX-deficient gliomas, offering a promising direction for future treatment strategies.
Published in
ATRX cooperates with TOP2B for replication fork stability and DNA damage response through G-quadruplex regulation
Pang Y, Cheng M, Wang J et al. · Nucleic acids research 2025 · PMID 40990248 · doi:10.1093/nar/gkaf939
This dataset
Open GSE275821 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 GSE275821_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 PRJNA1153037 and SRA study SRP529016. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40990248) ↗
Study design
12 conditions, mostly in triplicate
U87MG cells, Ctrl ×3 U87MG cells, siATRX ×3 U87MG cells, siTOP2B ×3 U87MG cells, DoubleKO ×3 PDCs, Ctrl_ATRX CUT&Tag, ×3 PDCs, CX5461_ATRX CUT&Tag, ×3 PDCs, Ctrl_TOP2B CUT&Tag, ×3 PDCs, CX5461_TOP2B CUT&Tag, ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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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