# Condensins regulate resection–dependent DNA double–strand break repair pathways in replicated chromatin

## TL;DR

This study shows that condensins help repair DNA breaks in the G2 phase of the cell cycle by regulating specific repair pathways.

## Contribution

The study identifies condensins as G2 phase-specific regulators of DNA repair pathways, a novel role in genome stability.

## Key findings

- Condensin depletion impairs DNA repair in G2 phase but not in G1 or S phase.
- Condensins regulate resection-dependent repair pathways like HR and alt-EJ in G2.
- Loss of condensins leads to chromatin decondensation and compromised DNA repair.

## Abstract

Condensins are key regulators of chromosome architecture and have emerging functions in DNA repair that are understudied. Here, we show that combined depletion of Condensin I and II in cell lines of normal and tumor origin selectively impairs DNA double-strand break (DSB) repair and the checkpoint response (DDR) specifically in the G2 phase of the cell cycle, with no detectable effects in G1 or S phase. Condensin knockdown increased cellular radiosensitivity and delayed in G2-phase, but not in asynchronous cells, the resolution of γH2AX and 53BP1 foci, indicating G2-specific defects in DSB repair. Mechanistically, condensin loss suppressed DNA end-resection and resection-dependent repair pathways, including homologous recombination (HR), single-strand annealing (SSA), and alternative end-joining (alt-EJ), but failed to significantly alter classical non-homologous end-joining (c-NHEJ). Reduced RAD51 and RPA70 foci formation in G2 confirmed inhibition of HR and DNA end resection. The G2 checkpoint was also compromised. Cytogenetic analysis revealed inhibition of chromosome break repair and visible chromatin decondensation, suggesting that condensins function to maintain an appropriate chromatin state for efficient DSB repair in G2-phase. These results identify for the first time condensins as G2 phase–specific regulators of genome stability by fine-tuning HR and other resection-dependent DSB repair pathways.

Graphical Abstract