CENPA
Encyclopedia
Centromere protein A, also known as CENPA, is a protein
which in humans is encoded by the CENPA gene
.
Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. The CENPA gene encodes a centromere protein which contains a histone H3
related histone fold domain that is required for targeting to the centromere. CENPA is proposed to be a component of a modified nucleosome
or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. Alternative splicing
results in multiple transcript variants encoding distinct isoforms.
In higher eukaryotes, the recruitment of CENP-A nucleosomes to existing centromeres is an epigenetic process, independent of the underlying DNA sequence. In S.pombe, de novo recruitment of the CENP-A to the centromere is believed to be controlled by "centromeric" heterochromatin
surrounding the centromere, and by a RNAi
mechanism. The RNAi is cut to form siRNA
; this complexes with the protein Chp1, which then binds the centromeric heterochromatin. This helps recruit other proteins, ultimately resulting in a protein complex that forms cohesin
between two sister chromatids
at the centromeric heterochromatin. This cohesin is believed to be essential in replacing the centromere H3 with CENP-A. CENP-A is one of the epigenetic changes that is believed to distinguish centromeric DNA from other DNA. Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the CENPA gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. The CENPA gene encodes a centromere protein which contains a histone H3
Histone H3
Histone H3 is one of the five main histone proteins 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 string' structure...
related histone fold domain that is required for targeting to the centromere. CENPA is proposed to be a component of a modified nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....
or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. Alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
results in multiple transcript variants encoding distinct isoforms.
In higher eukaryotes, the recruitment of CENP-A nucleosomes to existing centromeres is an epigenetic process, independent of the underlying DNA sequence. In S.pombe, de novo recruitment of the CENP-A to the centromere is believed to be controlled by "centromeric" heterochromatin
Heterochromatin
Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin...
surrounding the centromere, and by a RNAi
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
mechanism. The RNAi is cut to form siRNA
Sírna
Sírna Sáeglach , son of Dian mac Demal, son of Demal mac Rothechtaid, son of Rothechtaid mac Main, was, according to medieval Irish legend and historical tradition, a High King of Ireland...
; this complexes with the protein Chp1, which then binds the centromeric heterochromatin. This helps recruit other proteins, ultimately resulting in a protein complex that forms cohesin
Cohesin
Cohesin is a protein complex that regulates the separation of sister chromatids during cell division, either mitosis or meiosis.- Structure :...
between two sister chromatids
Sister chromatids
Sister chromatids are two identical copies of a chromatid connected by a centromere. Compare sister chromatids to homologous chromosomes, which are the two different copies of the same chromosome that diploid organisms inherit, one from each parent...
at the centromeric heterochromatin. This cohesin is believed to be essential in replacing the centromere H3 with CENP-A. CENP-A is one of the epigenetic changes that is believed to distinguish centromeric DNA from other DNA. Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.