Centromere protein F is a
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, respon ...
that in humans is encoded by the ''CENPF''
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 b ...
.
It is involved in
chromosome segregation
Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segrega ...
during
cell division
Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
. It also has a role in the orientation of
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 a ...
to
form
Form is the shape, visual appearance, or configuration of an object. In a wider sense, the form is the way something happens.
Form also refers to:
* Form (document), a document (printed or electronic) with spaces in which to write or enter dat ...
cellular
cilia
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
.
Function
CENPF is part of the
nuclear matrix
In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus after a specific method of chemical extraction. According to some it is somewhat analogous to the cell cytoskeleton. In contrast to the cytoskel ...
during the
G2 phase
G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the o ...
of the
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 sub ...
(the phase of rapid protein synthesis in preparation for
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maint ...
). In late G2, the protein forms part of the
kinetochore
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 ...
, a disc-shaped
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein ...
that allows the
centromere
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 ...
of two
sister chromatids
A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the dup ...
to attach to
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 a ...
(forming the
spindle apparatus
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 ...
) 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
Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall max ...
(the chromosome-dividing phase). In late anaphase, CENPF
localises to the spindle midzone, and in
telophase
Telophase () is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase (the nucleolus and nuclear membrane disintegrating) are reversed. As chromosomes reach the cell poles, a ...
(the cell-dividing phase) it localises to the
intercellular bridge
Cell junctions (or intercellular bridges) are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maint ...
. 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.
Microtubules are protein structures that are part of the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is comp ...
and are necessary for cells to have diverse, complex shapes and
migratory ability. They are made by the
centrosome
In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle pro ...
, 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
Form is the shape, visual appearance, or configuration of an object. In a wider sense, the form is the way something happens.
Form also refers to:
* Form (document), a document (printed or electronic) with spaces in which to write or enter dat ...
thin cellular projections called
cilia
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
. Most cilia are primary cilia, which are involved in
cell signalling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
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.
CENPF is thought to form either a
homodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
or
heterodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
.
Clinical significance
Mutations in both copies of ''CENPF'' cause
Strømme syndrome, characterised by microcephaly, eye abnormalities and apple-peel
jejunal atresia
Intestinal atresia is any congenital malformation of the structure of the intestine that causes bowel obstruction. The malformation can be a narrowing (stenosis), absence or malrotation of a portion of the intestine. These defects can either occur ...
.
Autoantibodies
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.
P ...
against CENPF have been found in patients with cancer or
graft-versus-host disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donor's immune system which remain wi ...
.
See also
* ''
CENPE
Centromere-associated protein E is a protein that in humans is encoded by the ''CENPE'' gene.
Centromere-associated protein E is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centromere-associ ...
''
*''
CENPJ''
* ''
CENPT''
References
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{{Chromosome genetics