Centromere protein A, also known as CENPA, 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, respo ...

which in humans is encoded by the ''CENPA''

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 ba ...

. CENPA is a

histone H3 Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a stri ...

variant Variant may refer to: In arts and entertainment * ''Variant'' (magazine), a former British cultural magazine * Variant cover, an issue of comic books with varying cover art * ''Variant'' (novel), a novel by Robison Wells * " The Variant", 2021 e ...

which is the critical factor determining 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 and ...

position(s) on each

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

in most

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s including humans.

Function

CENPA is a protein which

epigenetically In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

defines the position of the centromere on each chromosome, determining the position of kinetochore assembly and the final site of

sister chromatid 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 ...

cohesion during

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 mainta ...

. The CENPA protein is a histone H3 variant which replaces one or both canonical H3 histones in a subset of

nucleosome A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...

s within centromeric

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

. CENPA has the greatest sequence divergence of the histone H3 variants, with just 48% similarity to canonical histone H3, and has a highly diverged N-terminal tail that lacks many well characterised

histone modification In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn ar ...

sites including H3K4, H3K9 and H3K27. Unusually for a histone, CENPA nucleosomes are not loaded together with

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...

and are loaded at different

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 subs ...

stages in different organisms: G1 phase in human, M phase in drosophila, G2 in S. pombe. To orchestrate this specialised loading there are CENPA-specific histone chaperones:

HJURP Holliday junction recognition protein is a protein in humans that is encoded by the HJURP gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generatio ...

in human, CAL1 in

drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

and Scm3 in

S. 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 meas ...

. In most eukaryotes CENPA is loaded into large domains of highly repetitive satellite DNA. The position of CENPA within satellite DNA are

heritable Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic informa ...

at the protein level through a purely epigenetic mechanism. This means that the position of CENPA protein binding to the genome is copied upon

cell division Cell division is the process by which a parent cell (biology), 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 eukar ...

to the two daughter cells independent of the underlying DNA sequence. Under circumstances in which CENPA is lost from a chromosome a

fail-safe In engineering, a fail-safe is a design feature or practice that in the event of a specific type of failure, inherently responds in a way that will cause minimal or no harm to other equipment, to the environment or to people. Unlike inherent safe ...

mechanism has been described in human cells in which

CENPB 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. Function Centromere protein B is a highly conserved protein that fa ...

recruits CENPA via a satellite

DNA binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...

to repopulate the centromere with CENPA nucleosomes. CENPA interacts directly with the inner kinetochore through proteins including CENPC and

CENPN Centromere protein N is a protein that in humans is encoded by the ''CENPN'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''b ...

. Through this interaction the

microtubule 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 an ...

s are able to accurately segregate chromosomes during mitosis.

Function

References

External links

Further reading