| ORC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | ORC1 , HSORC1L, PARC1, origin recognition complex subunit 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 601902 MGI: 1328337 HomoloGene: 31221 GeneCards: ORC1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. [5] [6] It is closely related to CDC6, and both are the same protein in archaea. [7]
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 the pre-replication complex, which includes additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the origin recognition 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. [6]
ORC1 has been shown to interact with:
The origin of replication is a particular sequence in a genome at which replication is initiated. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semiconservative replication prior to cell division to ensure each daughter cell receives the full complement of chromosomes. This can either involve the replication of DNA in living organisms such as prokaryotes and eukaryotes, or that of DNA or RNA in viruses, such as double-stranded RNA viruses. Synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, organisms have evolved surprisingly divergent strategies that control replication onset. Although the specific replication origin organization structure and recognition varies from species to species, some common characteristics are shared.
A pre-replication complex (pre-RC) is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the same genetic information as the parent cell. Accordingly, formation of the pre-RC is a very important part of the cell cycle.
In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex that binds in all eukaryotes and archaea in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes. ORC is a central component for eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle.
Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.
The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas.
DNA replication licensing factor MCM3 is a protein that in humans is encoded by the MCM3 gene.
Replication factor C subunit 1 is a protein that in humans is encoded by the RFC1 gene.
CDT1 is a protein that in humans is encoded by the CDT1 gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle.
Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans.
Replication factor C subunit 4 is a protein that in humans is encoded by the RFC4 gene.
Replication factor C subunit 5 is a protein that in humans is encoded by the RFC5 gene.
Protein DBF4 homolog A is a protein that is encoded by the DBF4 gene in humans.
Histone acetyltransferase KAT7 is an enzyme that in humans is encoded by the KAT7 gene. It specifically acetylates H4 histones at the lysine12 residue (H4K12) and is necessary for origin licensing and DNA replication. KAT7 associates with origins of replication during G1 phase of the cell cycle through complexing with CDT1. Geminin is thought to inhibit the acetyltransferase activity of KAT7 when KAT7 and CDT1 are complexed together.
Origin recognition complex subunit 4 is a protein that in humans is encoded by the ORC4 (ORC4L) gene.
Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6 (ORC6L) gene.
Origin recognition complex subunit 5 is a protein that in humans is encoded by the ORC5 (ORC5L) gene.
Origin recognition complex subunit 3 is a protein that in humans is encoded by the ORC3 (ORC3L) gene.
Cdc6, or cell division cycle 6, is a protein in eukaryotic cells. It is mainly studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate S phase and mitosis. It is part of the pre-replicative complex (pre-RC) and is required for loading minichromosome maintenance (MCM) proteins onto the DNA, an essential step in the initiation of DNA synthesis. In addition, it is a member of the family of AAA+ ATPases and highly related to ORC1; both are the same protein in archaea.
In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle.
DNA re-replication is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers. To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being partially or fully rereplicated in a given cell cycle. These control mechanisms rely on cyclin-dependent kinase (CDK) activity. DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell cycle and DNA damage checkpoints. DNA rereplication must be strictly regulated to ensure that genomic information is faithfully transmitted through successive generations.
