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Dynamic loading and redistribution of the Mcm2‐7 helicase complex through the cell cycle
Author(s) -
Powell Sara K,
MacAlpine Heather K,
Prinz Joseph A,
Li Yulong,
Belsky Jason A,
MacAlpine David M
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201488307
Subject(s) - biology , redistribution (election) , helicase , microbiology and biotechnology , cell cycle , genetics , cell , biophysics , gene , rna , politics , political science , law
Eukaryotic replication origins are defined by the ORC ‐dependent loading of the Mcm2‐7 helicase complex onto chromatin in G1. Paradoxically, there is a vast excess of Mcm2‐7 relative to ORC assembled onto chromatin in G1. These excess Mcm2‐7 complexes exhibit little co‐localization with ORC or replication foci and can function as dormant origins. We dissected the mechanisms regulating the assembly and distribution of the Mcm2‐7 complex in the Drosophila genome. We found that in the absence of cyclin E/Cdk2 activity, there was a 10‐fold decrease in chromatin‐associated Mcm2‐7 relative to the levels found at the G1/S transition. The minimal amounts of Mcm2‐7 loaded in the absence of cyclin E/Cdk2 activity were strictly localized to ORC binding sites. In contrast, cyclin E/Cdk2 activity was required for maximal loading of Mcm2‐7 and a dramatic genome‐wide reorganization of the distribution of Mcm2‐7 that is shaped by active transcription. Thus, increasing cyclin E/Cdk2 activity over the course of G1 is not only critical for Mcm2‐7 loading, but also for the distribution of the Mcm2‐7 helicase prior to S‐phase entry.