GEO series

ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks

GSE312241 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 3 samples Submitted 2026/01/25 Platform GPL24676

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 3 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: 3 samples
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: ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaksNature communications · 2026

Summary (written by the submitters)

DNA double-strand breaks (DSBs) both pose threats to genome integrity and are commonly used for genome editing applications. Structural features of DSB ends play key roles in determining DNA repair pathway usage and outcomes during genome editing, but the cellular factors involved in these processes are only partially known. Through genome-wide CRISPRi screening, we identified ERCC6L2 as critical for repairing Cas12a-induced staggered DSBs but irrelevant for Cas9-induced blunt DSBs.

Read the full summary ↓

We show that ERCC6L2 acts as a protection factor for staggered DSBs with either 5’ or 3’ polarity, preventing large deletions and translocations stemming from DNA damage induced by Cas12a, TALENs, or dual Cas9 nicks. ERCC6L2 loss furthermore hyper-sensitizes cells to multiple staggered DSBs induced by promiscuous Cas12a activity or etoposide-induced TOP2 trapping. By combining genetics and biochemical reconstitution, we find that ERCC6L2 counteracts ATM-driven resection by binding and melting staggered DNA ends, thereby promoting accurate end joining. Our data reveal a protective role of ERCC6L2 in staggered DSB repair, which suggests the molecular underpinnings of pathology in patients with ERCC6L2 mutations and cautions against using overhang-inducing genome editing tools for their treatment.

Published in

ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks

Aird EJ, Serrano-Benitez A, Siegner SM et al. · Nature communications 2026 · PMID 41741470 · doi:10.1038/s41467-026-69843-w

This dataset

Open GSE312241 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 GSE312241_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 PRJNA1299151 and SRA study SRP605256. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41741470) ↗

Samples in this study

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+ 3 more — browse all 3 samples with per-sample file links →

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