Phase separation in DNA damage response: New insights into cancer development and therapy

Abstract

Phase separation, a process in which biomolecules segregate into distinct liquid-like compartments within cells, has recently been identified as a crucial regulator of various cellular functions, including the DNA damage response (DDR). Dysregulation of phase separation may contribute to genomic instability, oncogenesis, and tumor progression. However, the specific roles and mechanisms underlying phase separation remain largely elusive. This comprehensive review aims to elucidate the complex relationship between phase separation and the DDR in the context of cancer biology. We focus on the molecular mechanisms underlying phase separation and its role in orchestrating DDR signaling and repair processes. Additionally, we discuss how the dysregulation of phase separation in cancer cells impacts genome stability, tumorigenesis, and therapeutic responses. By leveraging the unique properties of phase separation in the DDR, researchers can potentially advance basic research and develop personalized cancer therapies targeting the dysregulated biomolecular condensates that drive tumorigenesis.