A Comprehensive Spatiotemporal Model Simulating 53BP1 Foci Dynamics during DNA Repair.

Abstract

p53-binding protein 1 (53BP1) exhibits liquid-liquid phase separation properties and forms DNA repair foci at DNA double-strand breaks (DSBs). While the dynamics of 53BP1 foci are essential for DSB signaling and repair, no current model can accurately simulate these processes. In this study, we developed a multi-scale computational framework that uses Monte Carlo methods to simulate the radiation-induced DSB distribution across the entire nucleus and 53BP1 foci dynamics, including foci formation, fission, and fusion. Our model incorporated the DSB clustering model to predict the formation of 53BP1 foci under various irradiation conditions, including fractionated irradiation. Additionally, our model can predict the temporal and spatial dynamics of 53BP1 foci, including their fission and fusion, as well as the repair dynamics of the foci. Validated against experimental dynamics under diverse conditions, this study established a unified model for 53BP1 foci dynamics, from formation to repair, providing a quantitative tool to investigate the spatiotemporal regulation of DNA damage repair.