Cdt1
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Cdt1
CDT1 (Chromatin licensing and DNA replication factor 1) 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. Role in pre-replication complexes The protein encoded by this gene is a key licensing factor in the assembly of pre-replication complexes (pre-RC), which occurs during the G1 phase of the cell cycle. In the assembly of pre-RCs, origin recognition complexes (ORC1-6) recognize and bind to DNA replication origins. CDT1, along with the protein CDC6, are then recruited to the forming pre-RC, followed by minichromosome maintenance complexes (MCM2-7). The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin, which inhibits it, and by SCFSKP2, which ubiquinates the protein to tag it for proteasomal degradation. This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cyc ...
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Pre-replication Complex
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. Components As organisms evolved and became increasingly more complex, so did their pre-RCs. The following is a summary of the components of the pre-RC amongst the different domains of life. In bacteria, the main component of the pre-RC is DnaA. The pre-RC is complete when DnaA occupies all of its binding sites within the bacterial origin of replication (oriC). The archaeal pre-RC is very different from the bacterial pre-RC and can serve as a simplified model of the eukaryotic pre-RC. It is composed of a single origin recognition complex (ORC) protein, Cd ...
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Origin Recognition Complex
In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) 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. ORC directs DNA replication throughout the genome and is required for its initiation. ORC and Noc3p bound at replication origins serve as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (a.k.a. Cdt1), and the Mcm2-Mcm7 complex. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase. Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including ...
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Geminin
Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the ''GMNN'' gene. A nuclear protein present in most eukaryotes and highly conserved across species, numerous functions have been elucidated for geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation. One example of its function is the inhibition of Cdt1. History Geminin was originally identified as an inhibitor of DNA replication and substrate of the anaphase-promoting complex. Coincidentally, geminin was also shown to expand the neural plate in the developing Xenopus embryo. Structure Geminin is a nuclear protein made up of about 200 amino acids, with a molecular weight of approximately 25 kDa. It contains an atypical leucine zipper coiled-coil domain. It has no known enzymatic activity nor DNA binding motifs. Function Cell cycle control Geminin is absent during G1 phase and accumulates through S, G2 pha ...
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Licensing Factor
A licensing factor is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. Licensing factors primarily occur in eukaryotic cells, since bacteria use simpler systems to initiate replication. However, many archaea use homologues of eukaryotic licensing factors to initiate replication. Function Origins of replication represent start sites for DNA replication and so their "firing" must be regulated to maintain the correct karyotype of the cell in question. The origins are required to fire only once per cell cycle, an observation that led to the postulated existence of licensing factors by biologists in the first place. If the origins were not carefully regulated then DNA replication could be restarted at that origin giving rise to multiple copies of a section of DNA. This could be damaging to cells and could have detrimental effects on the organism as a whole. The control that licensing factors exert over the cycle represents a f ...
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SKP2
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the ''SKP2'' gene. Structure and function Skp2 contains 424 residues in total with the ~40 amino acid F-box domain lying closer to the N-terminal region at the 94-140 position and the C-terminal region forming a concave surface consisting of ten leucine-rich repeats (LRRs). The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which often—but not always—recognize substrates in a phosphorylation-dependent manner. In this SCF complex, Skp2 acts as the substrate recognition factor. F-box Domain The F-box proteins are divided into three classes: Fbxws containing WD40 repeat domains, Fbxls containing leucine-rich repeats, and Fbxos containing either different protein–protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxls class. In addition to an F-box, this protein contains 10 ...
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Cell Cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division. In cells with nuclei ( eukaryotes, i.e., animal, plant, fungal, and protist cells), the cell cycle is divided into two main stages: interphase and the mitotic (M) phase (including mitosis and cytokinesis). During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the mitotic phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key steps ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Cdc6
Cell division control protein 6 homolog is a protein that in humans is encoded by the ''CDC6'' gene. The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in the cell nucleus during cell cycle phase G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during the cell cycle is regulated through its phosphorylation by cyclin-dependent kinases. Transcription of this protein was reported to be regulated in response to mitogenic signals through a transcriptional control mechanism involving E2F proteins. Interactions CDC6 has been shown to interact with ORC1L, ORC2L, Cyclin A2, PPP2R3B, MCM3, PPP2R3A, MCM7 and PSKH1. See also *Cdc6 Cell division control protein 6 homolog is a protein that in humans is encoded by the ''CDC6'' gene. The protein encoded ...
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Homology (biology)
In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of primates, the front flippers of whales and the forelegs of four-legged vertebrates like dogs and crocodiles are all derived from the same ancestral tetrapod structure. Evolutionary biology explains homologous structures adapted to different purposes as the result of descent with modification from a common ancestor. The term was first applied to biology in a non-evolutionary context by the anatomist Richard Owen in 1843. Homology was later explained by Charles Darwin's theory of evolution in 1859, but had been observed before this, from Aristotle onwards, and it was explicitly analysed by Pierre Belon in 1555. In developmental biology, organs that developed in the embryo in the same manner and from similar origins, such as from matching p ...
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Schizosaccharomyces Pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length. Its genome, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding genes and at least 450 non-coding RNAs. These cells maintain their shape by growing exclusively through the cell tips and divide by medial fission to produce two daughter cells of equal size, which makes them a powerful tool in cell cycle research. Fission yeast was isolated in 1893 by Paul Lindner from East African millet beer. The species name ''pombe'' is the Swahili word for beer. It was first developed as an experimental model in the 1950s: by Urs Leupold for studying genetics, and by Murdoch Mitchison for studying the cell cycle. Paul Nurse, a fission yeast ...
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Drosophila Melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Charles W. Woodworth's 1901 proposal of the use of this species as a model organism, ''D. melanogaster'' continues to be widely used for biological research in genetics, physiology, microbial pathogenesis, and life history evolution. As of 2017, five Nobel Prizes have been awarded to drosophilists for their work using the insect. ''D. melanogaster'' is typically used in research owing to its rapid life cycle, relatively simple genetics with only four pairs of chromosomes, and large number of offspring per generation. It was originally an African species, with all non-African lineages having a common origin. Its geographic range includes all continents, including islands. ''D. melanogaster'' is a common pest in homes, restaurants, and othe ...
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