Activation of the MCM2-7 Helicase by Association with Cdc45 and GINS proteins
By I. Ilves, T. Petojevic, James J Pesavento, M. Botchan. 2010
587 citations recorded by the source corpus.
Summary 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 pair-wise associations between 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.
Subfields: Cancer Research, Molecular Biology
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In Molecular Biology
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Citations in the corpus
- Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer (2011, background): “A large number of molecular players, including minichromosome maintenance (MCM) proteins, are involved in DNA replication [6-8].”
- DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7 (2020, background): “…demonstrate that our SM assays for CMG formation and helicase activation exhibit the outcomes and protein dependencies expected based on previous in vivo and ensemble in vitro studies (Kanemaki and Labib, 2006; Ilves et al., 2010; Heller et al., 2011; Tanaka et al., 2011; Yeeles et al., 2015).”
- CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol (epsilon}, and GINS in budding yeast. (2010, background): “The CMG complex purified to homogeneity shows a higher DNA helicase activity than Mcm alone (Ilves et al. 2010), suggesting that it works as a replicative DNA helicase.”