期刊
CELL REPORTS
卷 30, 期 10, 页码 3323-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.02.046
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资金
- Hong Kong Research Grants Council [GRF661713, 16103717]
- Science and Technology Innovation Bureau of Guangzhou Development District [CY2019-005]
- Hong Kong Baptist University, Research Committee, Initiation Grant - Faculty Niche Research Areas (IG-FNRA) 2018/19 [RC-FNRA-IG-18-19-SCM-01]
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.
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