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analyses show that orc1 allele newly identified is female sterile and possesses a unique feature of phenotypes that are distinct in different modes of DNA replication
Orc1 functioned in silencing before duplication and Orc1 and Sir2 (显示 SIRT1 蛋白) may have an ancient history of cooperating to generate chromatin structures, with Sir2 (显示 SIRT1 蛋白) deacetylating histones and Orc1 binding to these deacetylated nucleosomes
The opposing effects of ORC1 (represor) and CDC6 (显示 CDC6 蛋白) (gene activator) in controlling the level of Cyclin E (显示 CCNE1 蛋白) ensures genome stability and a mechanism for linking directly DNA replication and cell division commitment.
The authors have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1.
Orc1 acts as a nucleating center for origin recognition complex assembly and then pre-replication complex assembly by binding to mitotic chromosomes, followed by gradual removal from chromatin during the G1 phase.
ORC1 harbors a G-rich RNA/ssDNA-binding domain, which may be involved in the preferential binding to G-quadruplex-formable RNA/DNA by ORC. Structure modeling predicts the structural similarity between the G-rich RNA/ssDNA-binding domain of ORC1 and part of mammalian DNA methyltransferase 1 (显示 DNMT1 蛋白).
ORC1 associated with transcription start sites of coding or noncoding RNAs. Transcription levels at the ORC1 sites directly correlated with replication timing.
results identify the BAH (显示 ASPH 蛋白) domain as a novel methyl-lysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal aetiological role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism
Orc1 harbors a PACT (显示 RBBP6 蛋白) centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase (显示 CDK7 蛋白) activities of Cyclin E (显示 CCNE1 蛋白)-CDK2 (显示 CDK2 蛋白) and Cyclin A (显示 CCNA2 蛋白)-CDK2 (显示 CDK2 蛋白)
Data show that purified Epstein-Barr nuclear antigen 1 EBNA1 (显示 EBNA-1 蛋白) recruits purified Human Orc1 and Cdc6 (显示 CDC6 蛋白) onto replication origin oriP.
A lethal phenotype was seen in four individuals with compound heterozygous ORC1 mutations
As cells moved through the cell cycle, the local-ization of ORC1 shifted, suggesting changes in thelocalization of ORC-bound origin sequences.
mouse Orc1, Orc2, and Orc3 (显示 ORC3 蛋白) each exist in two alternative-splicing variants and naturally occurring Orc1B lacks a functional domain that is essential for nuclear translocation and proteasome-dependent degradation
The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the ORC complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MyST2/HBO1), a protein involved in control of transcription silencing. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
, origin recognition complex 1
, origin recognition complex subunit 1
, origin recognition complex, subunit 1 homolog
, replication control protein 1
, origin recognition complex protein 1
, origin recognition complex, subunit 1-like