Distinct and sequential re-replication barriers ensure precise genome duplication

摘要: DNA replication origin licensing, the process of MCM helicase loading, is an early essential step in and should be restricted to G1 phase avoid re-replication genome instability. Cdt1 a critical loading factor whose licensing activity must restrained after G1. We discovered that hyperphosphorylation during G2 M prevent damage, first example direct control by post-translational modification. This specifically requires Cyclin A/CDK1 occurs at cluster phosphorylation sites disordered linker region. Hyperphosphorylation interferes with Cdt1-MCM binding independently protein degradation or inhibition inhibitor, Geminin. At M-G1 transition, re-activated phosphatase 1-dependent dephosphorylation. propose distinct, non-redundant mechanisms act sequential relay from S through mitosis ensure once, only chromosome duplication.