Related Experiment Video
Updated: Aug 24, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53's double life: transactivation-independent repression of homologous recombination
Pascale Bertrand1, Yannick Saintigny, Bernard S Lopez
1UMR CEA/CNRS 217, CEA, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 18 route du panorama, 92265, Fontenay-aux-Roses, Cedex, France.
Abstract:
The tumor suppressor protein p53 controls cell cycle checkpoints and apoptosis via the transactivation of several genes. However, data from various laboratories suggest an additional role for p53: transcription-independent suppression of homologous recombination (HR). Genetic and physical interactions among p53, HR proteins (e.g. RAD51 and RAD54) and HR-DNA intermediates show that p53 acts directly on HR during the early and late steps of recombination. Complementary to the MSH2 mismatch-repair system, p53 appears to impair excess HR by controlling the minimal efficiency processing segment and by reversing recombination intermediates. By controlling the balance between the BLM and the RAD51 pathways, this direct role of p53 could maintain genome stability when replication forks are stalled at regions of DNA damage. In this article, we discuss the direct role of p53 on HR and the consequences for genome stability, tumor protection and speciation.
Insights
The tumor suppressor protein p53 directly suppresses homologous recombination (HR), a DNA repair process. This transcription-independent function helps maintain genome stability and protect against tumors.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The tumor suppressor protein p53 is known to regulate cell cycle checkpoints and apoptosis.
- Emerging evidence suggests p53 has additional roles beyond gene transactivation.
Purpose of the Study:
- To investigate the transcription-independent role of p53 in suppressing homologous recombination (HR).
- To elucidate the mechanisms by which p53 directly impacts HR and its implications for genome stability.
Main Methods:
- Analysis of genetic and physical interactions between p53 and HR proteins (RAD51, RAD54).
- Examination of p53's effect on early and late stages of DNA recombination.
- Comparison of p53's function with the MSH2 mismatch-repair system.
Main Results:
- p53 directly interacts with HR proteins and DNA intermediates, suppressing HR.
- p53 influences HR by controlling processing segments and reversing recombination intermediates.
- p53 balances BLM and RAD51 pathways to maintain genome stability during DNA damage.
Conclusions:
- p53 plays a direct, transcription-independent role in suppressing homologous recombination.
- This function of p53 is crucial for maintaining genome stability, particularly when replication forks are stalled.
- The direct suppression of HR by p53 has implications for tumor protection and potentially speciation.
Related Concept Videos
Abnormal Proliferation
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Negative Regulator Molecules
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Homologous Recombination

