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

Volume 11, Issue 7   April 1, 2012
Pages 1325 - 1339
http://dx.doi.org/10.4161/cc.19709
Keywords: DNA replication, Ipi2p and Ipi3p) complex, pre-replicative complex, replication licensing, the Rix 1 (Ipi1p
Authors: Lin Huo, Rentian Wu, Zhiling Yu, Yuanliang Zhai, Xiaoxia Yang, Tsz-choi Chan, Jeffrey T.F. Yeung, Junsuo Kan and Chun Liang

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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 G1 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.

Received: January 18, 2012; Accepted: February 14, 2012

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