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Human INT6 interacts with MCM7 and regulates its stability during S phase of the cell cycle

Oncogene volume 26, pages 5132–5144 (2007)Cite this article

Abstract

The mouse int6 gene is a frequent integration site of the mouse mammary tumor virus and INT6 silencing by RNA interference in HeLa cells causes an increased number of cells in the G2/M phases of the cell cycle, along with mitotic defects. In this report, we investigated the functional significance of the interaction between INT6 and MCM7, which was observed in a two-hybrid screen performed with INT6 as bait. It was found that proteasome inhibition strengthens interaction between both proteins and that INT6 stabilizes MCM7. Removal of MCM7 from chromatin as replication proceeds was accelerated in INT6-silenced cells and reduced amounts of protein were transiently observed, followed by a correction resulting from stimulation of mcm7 gene expression. Synchronized cells depleted for either INT6 or MCM7 display a reduction in thymidine incorporation and a reinforced association of RPA and claspin with chromatin. These data show that INT6 stabilizes chromatin-bound MCM7 and that alteration of this effect is associated with replication deficiency.

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Acknowledgements

We thank V Dixit, M Fujita, H Kimura and R Knippers for the generous gifts of plasmids and antibodies. We are also grateful to A Roisin for help with cell culture. This work was supported by a grant from the ‘Fondation pour la Recherche Médicale’ and by a fellowship from the ‘Ligue Nationale contre le cancer’ (SB).

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  1. Laboratoire de Biologie Moléculaire de la Cellule, UMR5161 CNRS/ENS de Lyon, IFR 128 Biosciences Lyon Gerland, Lyon cedex 07, Rhone, France

    S Buchsbaum, C Morris, V Bochard & P Jalinot

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  1. S Buchsbaum
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  2. C Morris
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  3. V Bochard
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Correspondence to P Jalinot.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Buchsbaum, S., Morris, C., Bochard, V. et al. Human INT6 interacts with MCM7 and regulates its stability during S phase of the cell cycle. Oncogene 26, 5132–5144 (2007). https://doi.org/10.1038/sj.onc.1210314

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