2020/03/01 by Aftab Amin, Rentian Wu, Man Hei Cheung +8 · 2 citations
Biochemistry, Genetics and Molecular Biology · #DNA Repair Mechanisms #Bacterial Genetics and Biotechnology #Genomics and Chromatin Dynamics
paper · pdf · doi:10.1016/j.celrep.2020.02.046
openalex publication_date 2020/03/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Eukaryotic DNA replication licensing is a prerequisite for, and plays a role in, regulating genome duplication that occurs exactly once per cell cycle. ORC (origin recognition complex) binds to and marks replication origins throughout the cell cycle and loads other replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs), completing replication licensing. However, how an asymmetric single-heterohexameric ORC structure loads the symmetric MCM (minichromosome maintenance) double hexamers is controversial, and importantly, it remains unknown when and how ORC proteins associate with the newly replicated origins to protect them from invasion by histones. Here, we report an essential and cell-cycle-dependent ORC "dimerization cycle" that plays three fundamental roles in the regulation of DNA replication: providing a symmetric platform to load the symmetric pre-RCs, marking and protecting the nascent sister replication origins for the next licensing, and playing a crucial role to prevent origin re-licensing within the same cell cycle.