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Updated: Jul 31, 2025

Preparation of the Mgm101 Recombination Protein by MBP-based Tagging Strategy
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The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair

Jimin Li1, Jingyu Zhao1, Xiaoli Gan1

  • 1Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Frontier Science Centre of Immunology and Metabolism, Wuhan University, Wuhan 430072, China.

Proceedings of the National Academy of Sciences of the United States of America
|May 8, 2023
PubMed

Insights

Replication protein A (RPA) recruits Ring finger protein 20 (RNF20) to centromeres and DNA breaks, ensuring genome stability. This RPA-RNF20 pathway is crucial for chromosome segregation and DNA repair, preventing genomic instability.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Ring finger protein 20 (RNF20) and its mediated histone H2B monoubiquitination (H2Bub) are vital for chromosome segregation and DNA repair.
  • The precise mechanisms and activation of the RNF20-H2Bub pathway in maintaining genome stability were previously unclear.

Purpose of the Study:

  • To elucidate the function and mechanism of RNF20-H2Bub in chromosome segregation.
  • To understand how this pathway is activated to preserve genome stability.

Main Methods:

  • Investigated the interaction between Replication protein A (RPA) and RNF20 during the cell cycle.
  • Analyzed the recruitment of RNF20 to centromeres and DNA breaks.
  • Assessed the impact of disrupting the RPA-RNF20 interaction on chromosome segregation and DNA repair.

Main Results:

  • RPA interacts with RNF20 in S and G2/M phases, recruiting it to centromeres via R-loops and to DNA breaks.
  • Disruption of RPA-RNF20 interaction or RNF20 depletion leads to increased chromosome segregation errors and impaired DNA repair (BRCA1, RAD51 loading, homologous recombination).
  • The RPA-RNF20 pathway promotes H2Bub, H3K4 dimethylation, SNF2H recruitment, Aurora B kinase activation, and DNA repair protein loading.

Conclusions:

  • The RPA-RNF20-SNF2H cascade is essential for genome stability.
  • This pathway couples H2Bub to proper chromosome segregation and efficient DNA repair.
Keywords:
H2B ubiquitinationRNF20RPAchromosome segregationhomologous recombination

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