DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis.

ABSTRACT: Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate to maintain hematopoiesis, increasing their susceptibility to DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, and prevent aging-driven dysregulation are unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar DNA replication fork reversal biochemical functions, Zranb3 and Smarcal1, have surprisingly specialized roles in distinct HSPC populations. While both proteins actively mitigate replication stress and prevent DNA damage and breaks during lifelong hematopoiesis, the loss of either resulted in distinct biochemical and biological consequences. Notably, defective long-term

SUBMITTER: Kushinsky S 

PROVIDER: S-EPMC11561652 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature