The labs of Emilio Lecona Sagrado and Juan Méndez published a new study uncovering a novel regulatory mechanism in DNA replication involving VPC/p97.
Their research reveals that VPC/p97-mediated extraction of DNA Pol α/primase from chromatin restricts overactivation of the ATR checkpoint pathway during unperturbed DNA replication.
Key findings:
- VCP/p97 removes Pol α/primase from chromatin to suppress TOPBP1-dependent ATR activation under unperturbed replication conditions.
- Inhibition of VCP/p97 leads to the accumulation of Pol α/primase on chromatin, enhancing ATR signalling and triggering cell cycle arrest at G2/M.
- VCP/p97 acts as a safeguard against replication stress overreaction.
- Basal ATR and CHK1 activity in S phase partly depend on the priming action of Pol α/primase.
