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Updated: Jan 27, 2026

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
08:53

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method

Published on: May 2, 2025

950

Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation

Eva Malacaria1, Giusj Monia Pugliese1, Masayoshi Honda2

  • 1Mechanisms, Biomarkers and Models Unit, Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.

Nature Communications
|March 31, 2019
PubMed

Insights

RAD52 safeguards genome stability by preventing excessive degradation of stalled replication forks. It acts as a gatekeeper, limiting fork remodelling and supporting DNA repair proteins like RAD51 and BRCA2.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Replication fork stability is crucial for genome integrity.
  • Uncontrolled degradation of stalled forks can lead to genomic instability.

Purpose of the Study:

  • To investigate the physiological role of RAD52 at stalled replication forks.
  • To elucidate the mechanism by which RAD52 influences fork stability and genome integrity.

Main Methods:

  • Human cell models with RAD52 depletion.
  • Small-molecule inhibitor targeting the RAD52-ssDNA interaction.
  • In vitro and single-molecule analyses.
  • Assays for replication restart, fork degradation, and chromosome instability.

Main Results:

  • RAD52 prevents excessive degradation of reversed replication forks by MRE11.
  • RAD52 binds to stalled forks, promotes occlusion, and counteracts SMARCAL1 loading.
  • Loss of RAD52 function leads to defective replication restart and chromosome instability.
  • RAD52 inhibition increases reliance on RAD51 for replication completion and viability.

Conclusions:

  • RAD52 acts as a gatekeeper, limiting excessive remodelling of stalled replication forks.
  • RAD52 indirectly assists RAD51 and BRCA2 in protecting forks from degradation.
  • RAD52 plays a vital role in preventing genome instability during replication stress.

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