Safeguarding the genome by maintaining quiescence is crucial for the preservation of hematopoietic stem cell (HSC) function and for the prevention of leukemia.However, quiescent HSCs conversely accrue more DNA damage than their progeny during aging and after exposure to ionizing radiation (IR) and are susceptible to the induction of genomic instability under genotoxic stress.The mechanism underlying this discrepancy is largely unknown.