GEO series

Comprehensive Interrogation of Synthetic Lethality in the DNA Damage Response

GSE236062 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 25 samples Submitted 2025/02/03 Platform GPL30173

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 25 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: 25 samples: 17 distinct titles, 4 of them repeatedGroups 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: Comprehensive interrogation of synthetic lethality in the DNA damage responseNature · 2025

Summary (written by the submitters)

The DNA damage response (DDR) is a multi-faceted network of pathways that preserves genome stability. Unraveling the complementary interplay between these pathways remains a challenge. Here, we comprehensively mapped genetic interactions for all core DDR genes using combinatorial CRISPRi screening. We discovered myriad new connections, including interactions between cancer genes and small molecule targets.

Read the full summary ↓

We focused on two of the strongest interactions: FEN1/LIG1:WDR48 and FANCM:SMARCAL1. First, we found that WDR48 works with USP1 to restrain overactive translesion synthesis in FEN1/LIG1-deficient cells, and that a preclinical inhibitor of USP1 specifically kills FEN1-deficient cells. Second, we found that SMARCAL1 and FANCM suppress DNA double-strand break (DSB) formation at TA-rich repeats in late-replicating regions that otherwise escape into mitosis and cause nuclear fragmentation. Our dataset provides a springboard for further mechanistic investigations into connections between DDR factors and suggests multiple interactions that could be exploited in cancer therapy.

Published in

Comprehensive interrogation of synthetic lethality in the DNA damage response

Fielden J, Siegner SM, Gallagher DN et al. · Nature 2025 · PMID 40205037 · doi:10.1038/s41586-025-08815-4

This dataset

Open GSE236062 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 GSE236062_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 PRJNA988524 and SRA study SRP446377. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40205037) ↗

Study design

17 distinct titles, 4 of them repeated

Double-SDel-sgFM ×3 SMARCAL1 KO ×3 FANCM-depleted ×3 RPE1 WT ×3

How we read this: Read from 25 sample titles: 17 distinct titles with little repetition. 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

GSM7517666 Double-SDel-sgFM rep1
GSM7517667 Double-SDel-sgFM rep2
GSM7517668 Double-SDel-sgFM rep3
GSM7517669 SMARCAL1 KO rep1
GSM7517670 SMARCAL1 KO rep2
GSM7517671 SMARCAL1 KO rep3
GSM7517672 FANCM-depleted rep1
GSM7517673 FANCM-depleted rep2
GSM7517674 FANCM-depleted rep3
GSM7517675 RPE1 WT rep1
GSM7517676 RPE1 WT rep2
GSM7517677 RPE1 WT rep3
GSM8350313 FANCM_WT rep1
GSM8350314 FANCM_SMARCAL1KO rep1
GSM8350315 SMARCAL1_WT rep1
GSM8350316 SMARCAL1_FANCMKO rep1
GSM8350317 WT_X rep1
GSM8350318 SMARCAL1KO_X rep1
GSM8350319 sgFANCM_X rep1
GSM8350320 SMARCAL1KOsgFANCM_X rep1
GSM8350321 doubles rep1
GSM8350322 doubles_ERCC1 rep1
GSM8350323 doubles_ERCC4 rep1
GSM8350324 doubles_GEN1 rep1
GSM8350325 doubles_MUS81 rep1

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