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Pre-initiation complex assembly functions as a molecular switch that splits the Mcm2-7 double hexamer.
Mayumi Miyazawa-Onami1, Hiroyuki Araki1,2, Seiji Tanaka3,2,4
1Division of Microbial Genetics, National Institute of Genetics, Mishima, Shizuoka, Japan.
EMBO Reports
|August 19, 2017
Summary
Researchers confirmed the pre-initiation complex (pre-IC) in yeast DNA replication. This intermediate splits the Mcm2-7 double hexamer during firing, acting as a molecular switch.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Eukaryotic DNA replication initiation involves licensing and firing.
- The Mcm2-7 complex is loaded during licensing and activated during firing.
- A transient pre-initiation complex (pre-IC) has been hypothesized but not confirmed.
Purpose of the Study:
- To confirm the existence and characterize the assembly of the pre-IC during DNA replication firing.
- To investigate the role of firing factors in pre-IC formation.
Main Methods:
- Systematic chromatin immunoprecipitation in Saccharomyces cerevisiae.
- Analysis of Mcm2-7 complex behavior during replication firing.
Main Results:
- Confirmed the assembly of a distinct pre-IC intermediate during replication firing.
- Pre-IC assembly occurs independently of Mcm10 but depends on other firing factors activated by cyclin-dependent kinase.
- In the pre-IC, the Mcm2-7 double hexamer separates into single hexamers.
Conclusions:
- Pre-IC assembly is a confirmed intermediate in eukaryotic DNA replication firing.
- Pre-IC formation acts as an all-or-nothing switch, splitting the Mcm2-7 double hexamer.
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