ArticleGenes & development2012
Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 65 citations in OpenAlex.
- Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions.Nature communications · 2025Article
- Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates.Nature communications · 2025Article
- The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome.European journal of human genetics : EJHG · 2023Review
- Distinct roles of Arabidopsis ORC1 proteins in DNA replication and heterochromatic H3K27me1 deposition.Nature communications · 2023Article
- Orc6 is a component of the replication fork and enables efficient mismatch repair.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.Molecular cell · 2021Article
- Article
- DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1.Life sciences · 2020Article
- Origin Recognition Complex (ORC) Evolution Is Influenced by Global Gene Duplication/Loss Patterns in Eukaryotic Genomes.Genome biology and evolution · 2020Article
- Tissue-Specific DNA Replication Defects inGenetics · 2020Article
- Structural basis for the ORC1-Cyclin A association.Protein science : a publication of the Protein Society · 2019Article
- Molecular mechanism and potential target indication of TAK-931, a novel CDC7-selective inhibitor.Science advances · 2019Article
- Analysis of cilia dysfunction phenotypes in zebrafish embryos depleted of Origin recognition complex factors.European journal of human genetics : EJHG · 2019Article
- Review
- Controlling centriole numbers: Geminin family members as master regulators of centriole amplification and multiciliogenesis.Chromosoma · 2018Review
- The SKP1-Cullin-F-box E3 ligase βTrCP and CDK2 cooperate to control STIL abundance and centriole number.Open biology · 2018Article
- Nonreplicative functions of the origin recognition complex.Nucleus (Austin, Tex.) · 2018Review
- The dNTP triphosphohydrolase activity of SAMHD1 persists during S-phase when the enzyme is phosphorylated at T592.Cell cycle (Georgetown, Tex.) · 2018Article
- Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.PLoS genetics · 2017Article
- Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development.DNA repair · 2017Review
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Abstract
Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.
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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.