The Rix1 (Ipi1p-2p-3p) complex is a critical determinant of DNA replication licensing independent of their roles in ribosome biogenesis

Lin Huo, Rentian Wu, Zhiling YU, Yuanliang Zhai, Xiaoxia Yang, Tsz Choi Chan, Jeffrey T.F. Yeung, Junsuo Kan, Chun Liang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Several replication-initiation proteins are assembled stepwise onto replicators to form pre-replicative complexes (pre-RCs) to license eukaryotic DNA replication. We performed a yeast functional proteomic screen and identified the Rix1 complex members (Ipi1p-Ipi2p/Rix1-Ipi3p) as pre-RC components and critical determinants of replication licensing and replication-initiation frequency. Ipi3p interacts with pre-RC proteins, binds chromatin predominantly at ARS sequences in a cell cycle-regulated and ORC- and Noc3p-dependent manner and is required for loading Cdc6p, Cdt1p and MCM onto chromatin to form pre-RC during the M-to-G1 transition and for pre-RC maintenance in G 1 phase, independent of its role in ribosome biogenesis. Moreover, Ipi1p and Ipi2p, but not other ribosome biogenesis proteins Rea1p and Utp1p, are also required for pre-RC formation and maintenance, and Ipi1p, -2p and -3p are interdependent for their chromatin association and function in pre-RC formation. These results establish a new framework for the hierarchy of pre-RC proteins, where the Ipi1p-2p-3p complex provides a critical link between ORC-Noc3p and Cdc6p-Cdt1p-MCM in replication licensing.

Original languageEnglish
Pages (from-to)1325-1339
Number of pages15
JournalCell Cycle
Volume11
Issue number7
DOIs
Publication statusPublished - 1 Apr 2012

Scopus Subject Areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

User-Defined Keywords

  • DNA replication
  • Pre-replicative complex
  • Replication licensing
  • The Rix 1 (Ipi1p, Ipi2p and Ipi3p) complex

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