Activation of the MCM2-7 Helicase by Association with Cdc45 and GINS Proteins
| Autor: | Tatjana Petojevic, James J. Pesavento, Michael R. Botchan, Ivar Ilves |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
DNA Replication
Molecular Sequence Data Cell Cycle Proteins Models Biological Article chemistry.chemical_compound Adenosine Triphosphate Control of chromosome duplication Animals Drosophila Proteins Amino Acid Sequence Molecular Biology CMG complex biology Circular bacterial chromosome DNA replication Helicase DNA Cell Biology RNA Helicase A GINS Enzyme Activation Drosophila melanogaster chemistry Biochemistry biology.protein Sequence Alignment |
| Zdroj: | Molecular Cell. 37:247-258 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2009.12.030 |
| Popis: | MCM2-7 proteins provide essential helicase functions in eukaryotes at chromosomal DNA replication forks. During the G1 phase of the cell cycle, they remain loaded on DNA but are inactive. We have used recombinant methods to show that the Drosophila MCM2-7 helicase is activated in complex with Cdc45 and the four GINS proteins (CMG complex). Biochemical activities of the MCM AAA+ motor are altered and enhanced through such associations: ATP hydrolysis rates are elevated by two orders of magnitude, helicase activity is robust on circular templates, and affinity for DNA substrates is improved. The GINS proteins contribute to DNA substrate affinity and bind specifically to the MCM4 subunit. All pairwise associations among GINS, MCMs, and Cdc45 were detected, but tight association takes place only in the CMG. The onset of DNA replication and unwinding may thus occur through allosteric changes in MCM2-7 affected by the association of these ancillary factors. |
| Databáze: | OpenAIRE |
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