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The interacting domains of hCdt1 and hMcm6 involved in the chromatin loading of the MCM complex in human cells

Authors Zhang, Jing HKUST affiliated (currently or previously).
Yu, Lan HKUST affiliated (currently or previously).
Wu, Xing HKUST affiliated (currently or previously).
Zou, Lan HKUST affiliated (currently or previously)
Sou, K.K.L. HKUST affiliated (currently or previously)
Wei, Zhun HKUST affiliated (currently or previously)
Cheng, Xue HKUST affiliated (currently or previously)
Zhu, Guang View this author's profile
Liang, Chun View this author's profile
Issue Date 2010
Source Cell Cycle , v. 9, (24), 2010, p. 4848-4857
Summary The stepwise assembly of pre-replicative complexes (pre-RCs) is essential for the initiation of DNA replication. Cdt1, a component of the pre-RC, is required for the loading of the minichromosome maintenance (MCM) complex onto chromatin. Cdt1 physically interacts with the MCM complex, and this interaction mainly occurs between Cdt1 and Mcm6 in human cells. Here we show by yeast two-hybrid analysis, co-immunoprecipitation and GST pull-down assays that the extreme C-terminal region of hMcm6 (a.a. 708-821) interacts with a short C-terminal region in hCdt1 (a.a. 392-471), while the large N-terminal part of hMcm6 (a.a. 1-707) interacts with some other MCM subunits. Furthermore, our functional studies show that ectopic expression of either of the interacting domains of hCdt1 and hMcm6 in human cells reduces chromatin association of the MCM complex and DNA replication, inhibits cell proliferation and leads to cell apoptosis. These dominant negative effects indicate that the interaction between hCdt1 and hMcm6 through their interacting domains we identified is the key for hCdt1 in facilitating the MCM hetero-hexamer to load onto chromatin for replication licensing. The newly indentified interacting domains of hCdt1 and hMcm6 may become targets for identification of novel anticancer drugs. © 2010 Landes Bioscience.
ISSN 1538-4101
Rights Copyright 2010 © Landes Bioscience
Language English
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