ArticleThe Journal of biological chemistry2007
Cdc6 ATPase activity regulates ORC x Cdc6 stability and the selection of specific DNA sequences as origins of DNA replication.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 100 citations in OpenAlex.
- A lethal ORC ATPase mutation is suppressed by alterations in ORC and RNA Pol II transcription components.PloS one · 2026Article
- Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions.Nature communications · 2025Article
- Mechanisms for licensing origins of DNA replication in eukaryotic cells.Nature structural & molecular biology · 2025Review
- Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates.Nature communications · 2025Article
- MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.Nature communications · 2025Article
- Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing.Nature communications · 2024Article
- A chromatinized origin reduces the mobility of ORC and MCM through interactions and spatial constraint.Nature communications · 2023Article
- Differential condensation of sister chromatids acts with Cdc6 to ensure asynchronous S-phase entry in Drosophila male germline stem cell lineage.Developmental cell · 2022Article
- A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6.Nature communications · 2022Article
- The structure of ORC-Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6.Nature communications · 2021Article
- Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.Molecular cell · 2021Article
- DNA replication origins retain mobile licensing proteins.Nature communications · 2021Article
- Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6.Nature communications · 2020Article
- Physical Basis for the Loading of a Bacterial Replicative Helicase onto DNA.Molecular cell · 2019Article
- Article
- A structural view of the initiators for chromosome replication.Current opinion in structural biology · 2018Review
- LIM and cysteine-rich domains 1 is required for thrombin-induced smooth muscle cell proliferation and promotes atherogenesis.The Journal of biological chemistry · 2018Article
- From structure to mechanism-understanding initiation of DNA replication.Genes & development · 2017Review
- Mechanisms and regulation of DNA replication initiation in eukaryotes.Critical reviews in biochemistry and molecular biology · 2017Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
DNA replication, as with all macromolecular synthesis steps, is controlled in part at the level of initiation. Although the origin recognition complex (ORC) binds to origins of DNA replication, it does not solely determine their location. To initiate DNA replication ORC requires Cdc6 to target initiation to specific DNA sequences in chromosomes and with Cdt1 loads the ring-shaped mini-chromosome maintenance (MCM) 2-7 DNA helicase component onto DNA. ORC and Cdc6 combine to form a ring-shaped complex that contains six AAA+ subunits. ORC and Cdc6 ATPase mutants are defective in MCM loading, and ORC ATPase mutants have reduced activity in ORC x Cdc6 x DNA complex formation. Here we analyzed the role of the Cdc6 ATPase on ORC x Cdc6 complex stability in the presence or absence of specific DNA sequences. Cdc6 ATPase is activated by ORC, regulates ORC x Cdc6 complex stability, and is suppressed by origin DNA. Mutations in the conserved origin A element, and to a lesser extent mutations in the B1 and B2 elements, induce Cdc6 ATPase activity and prevent stable ORC x Cdc6 formation. By analyzing ORC x Cdc6 complex stability on various DNAs, we demonstrated that specific DNA sequences control the rate of Cdc6 ATPase, which in turn controls the rate of Cdc6 dissociation from the ORC x Cdc6 x DNA complex. We propose a mechanism explaining how Cdc6 ATPase activity promotes origin DNA sequence specificity; on DNA that lacks origin activity, Cdc6 ATPase promotes dissociation of Cdc6, whereas origin DNA down-regulates Cdc6 ATPase resulting in a stable ORC x Cdc6 x DNA complex, which can then promote MCM loading. This model has relevance for origin specificity in higher eukaryotes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.