Centromere protein F is a protein that in humans is encoded by the CENPF gene. [5] [6] [7] It is involved in chromosome segregation during cell division. It also has a role in the orientation of microtubules to form cellular cilia. [8] [9]
Centromere protein F is a protein that in humans is encoded by the CENPF gene. [5] [6] [7] It is involved in chromosome segregation during cell division. It also has a role in the orientation of microtubules to form cellular cilia. [8] [9]
CENPF is part of the nuclear matrix during the G2 phase of the cell cycle (the phase of rapid protein synthesis in preparation for mitosis). In late G2, the protein forms part of the kinetochore, a disc-shaped protein complex that allows the centromere of two sister chromatids to attach to microtubules (forming the spindle apparatus) in order for the microtubules to pull them apart in the process of dividing the cell. It remains part of the kinetochore through early anaphase (the chromosome-dividing phase). In late anaphase, CENPF localises to the spindle midzone, and in telophase (the cell-dividing phase) it localises to the intercellular bridge. It is thought to be subsequently degraded. Mutations in CENPF lead to impaired cell division during early development. Mitosis has been found to take longer when the gene is mutated. [8] [9]
Microtubules are protein structures that are part of the cytoskeleton and are necessary for cells to have diverse, complex shapes and migratory ability. They are made by the centrosome, which contains a pair of cylindrical centrioles at right-angles to each other. Before division, CENPF localises at the end of one of the centrioles (the mother centriole) in order to orient microtubules correctly to form thin cellular projections called cilia. Most cilia are primary cilia, which are involved in cell signalling to trigger migration, division or differentiation. Mutations in CENPF disrupt this ability to form cilia; cilia have been found to be fewer in number and shorter when the gene is mutated. [8] [10]
CENPF is thought to form either a homodimer or heterodimer.
Mutations in both copies of CENPF cause Strømme syndrome, characterised by microcephaly, eye abnormalities and apple-peel jejunal atresia. [11] Autoantibodies against CENPF have been found in patients with cancer or graft-versus-host disease. [7]
The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers attach to the centromere via the kinetochore.
In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.
A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.
Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.
Centromere protein B also known as major centromere autoantigen B is an autoantigen protein of the cell nucleus. In humans, centromere protein B is encoded by the CENPB gene.
Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 is an enzyme that in humans is encoded by the BUB1 gene.
Centromere protein A, also known as CENPA, is a protein which in humans is encoded by the CENPA gene. CENPA is a histone H3 variant which is the critical factor determining the kinetochore position(s) on each chromosome in most eukaryotes including humans.
Kinetochore protein NDC80 homolog is a protein that in humans is encoded by the NDC80 gene.
Inner centromere protein is a protein that in humans is encoded by the INCENP gene.
Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.
Disks large-associated protein 5 (DAP-5) also known as discs large homolog 7 (DLG7) or hepatoma up-regulated protein (HURP) is a protein that in humans is encoded by the DLGAP5 gene.
Kinesin-like protein KIF2C is a protein that in humans is encoded by the KIF2C gene.
Centromere protein C 1 is a protein that in humans is encoded by the CENPC1 gene.
Kinetochore protein Nuf2 is a protein that in humans is encoded by the NUF2 gene.
Dual specificity protein phosphatase CDC14A is an enzyme that in humans is encoded by the CDC14A gene.
Centromere/kinetochore protein zw10 homolog is a protein that in humans is encoded by the ZW10 gene. This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. The encoded protein binds to centromeres during the prophase, metaphase, and early anaphase cell division stages and to kinetochore microtubules during metaphase.
Centromere protein H is a protein that in humans is encoded by the CENPH gene.
Strømme syndrome is a very rare autosomal recessive genetic condition characterised by intestinal atresia, eye abnormalities and microcephaly. The intestinal atresia is of the "apple-peel" type, in which the remaining intestine is twisted around its main artery. The front third of the eye is typically underdeveloped, and there is usually moderate developmental delay. Less common features include an atrial septal defect, increased muscle tone or skeletal abnormalities. Physical features may include short stature, large, low-set ears, a small jaw, a large mouth, epicanthic folds, or fine, sparse hair.
Tim J. Yen is an American molecular biologist and cancer biologist. Yen is currently director of the Biological Imaging Facility at Fox Chase Cancer Center in Philadelphia, Pennsylvania. Yen is known for pioneering work in the field of mitosis.