From rest to repair: Safeguarding genomic integrity in quiescent cells

Abstract

Quiescence is an important non-pathological state in which cells pause cell cycle progression temporarily, sometimes for decades, until they receive appropriate proliferative stimuli. Quiescent cells make up a significant proportion of the body, and maintaining genomic integrity during quiescence is crucial for tissue structure and function. While cells in quiescence are spared from DNA damage associated with DNA replication or mitosis, they are still exposed to various sources of endogenous DNA damage, including those induced by normal transcription and metabolism. As such, it is vital that cells retain their capacity to effectively repair lesions that may occur and return to the cell cycle without losing their cellular properties. Notably, while DNA repair pathways are often found to be downregulated in quiescent cells, emerging evidence suggests the presence of active or differentially regulated repair mechanisms. This review aims to provide a current understanding of DNA repair processes during quiescence in mammalian systems and sheds light on the potential pathological consequences of inefficient or inaccurate repair in quiescent cells.