An essential Noc3p dimerization cycle mediates ORC double-hexamer formation in replication licensing

Aftab Amin, Rentian Wu, Muhammad Ajmal Khan, Man Hei Cheung, Yanting Liang, Changdong Liu, Guang Zhu, Zhi Ling Yu*, Chun Liang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


Replication licensing, a prerequisite of DNA replication, helps to ensure once-per-cell-cycle genome duplication. Some DNA replication-initiation proteins are sequentially loaded onto replication origins to form pre-replicative complexes (pre-RCs). ORC and Noc3p bind replication origins throughout the cell cycle, providing a platform for pre-RC assembly. We previously reported that cell cycle–dependent ORC dimerization is essential for the chromatin loading of the symmetric MCM double-hexamers. Here, we used Saccharomyces cerevisiae separation-of-function NOC3 mutants to confirm the separable roles of Noc3p in DNA replication and ribosome biogenesis. We also show that an essential and cell cycle–dependent Noc3p dimerization cycle regulates the ORC dimerization cycle. Noc3p dimerizes at the M-to-G1 transition and de-dimerizes in S-phase. The Noc3p dimerization cycle coupled with the ORC dimerization cycle enables replication licensing, protects nascent sister replication origins after replication initiation, and prevents re-replication. This study has revealed a new mechanism of replication licensing and elucidated the molecular mechanism of Noc3p as a mediator of ORC dimerization in pre-RC formation.

Original languageEnglish
Article numbere202201594
Number of pages22
JournalLife Science Alliance
Issue number3
Publication statusPublished - Mar 2023

Scopus Subject Areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis


Dive into the research topics of 'An essential Noc3p dimerization cycle mediates ORC double-hexamer formation in replication licensing'. Together they form a unique fingerprint.

Cite this