Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription

Hossain, M., Stillman, B. (2016) Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription. Elife, 5. ISSN 2050-084X (Electronic)2050-084X (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/27458800
DOI: 10.7554/eLife.12785

Abstract

Newly-born cells either continue to proliferate or exit the cell division cycle. This decision involves delaying expression of Cyclin E that promotes DNA replication. ORC1, the Origin Recognition Complex (ORC) large subunit, is inherited into newly-born cells after it binds to condensing chromosomes during the preceding mitosis. We demonstrate that ORC1 represses Cyclin E gene (CCNE1) transcription, an E2F1 activated gene that is also repressed by the Retinoblastoma (RB) protein. ORC1 binds to RB, the histone methyltransferase SUV39H1 and to its repressive histone H3K9me3 mark. ORC1 cooperates with SUV39H1 and RB protein to repress E2F1-dependent CCNE1 transcription. In contrast, the ORC1-related replication protein CDC6 binds Cyclin E-CDK2 kinase and in a feedback loop removes RB from ORC1, thereby hyper-activating CCNE1 transcription. The opposing effects of ORC1 and CDC6 in controlling the level of Cyclin E ensures genome stability and a mechanism for linking directly DNA replication and cell division commitment.

Item Type: Paper
Uncontrolled Keywords: biochemistry chromosomes genes human
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > origin recognition complex
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: Matt Covey
Date Deposited: 28 Jul 2016 19:11
Last Modified: 08 Sep 2017 21:02
PMCID: PMC4987141
Related URLs:
Dataset ID:
URI: http://repository.cshl.edu/id/eprint/33049

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