A
centromere is a region of
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
typically found near the middle of a
chromosomeA chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions...
where two identical
sister chromatidsSister chromatids are identical copies of a chromosome 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...
come in contact. It is involved in
cell divisionCell division is a process by which a cell, called the parent cell, divides into two or more cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing...
as the point of
mitotic spindleIn cell biology, the spindle apparatus is the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryotic cells...
.
Function
The centromeres are, together with telomeres and origins of replication, one of the essential parts of any eukaryotic chromosome. The centromere usually contains specific types of
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
sequences which are in higher eukaryotes typically tandem repetitive sequences, often called "
satellite DNASatellite DNA consists of highly repetitive DNA, and is so called because repetitions of a short DNA sequence tend to produce a different frequency of the nucleotides adenine, cytosine, guanine and thymine, and thus have a different density from bulk DNA - such that they form a second or...
". These sequences bind specific proteins called "cen"-Proteins. During mitosis the centromeres can be identified in particular during the metaphase stage as a constriction at the chromosome. At this centromeric constriction the two mostly identical halves of the chromosome, the sister chromatids, are held together until late metaphase. During mitotic division, a transient structure called
kinetochore is formed on top of the centromeres. The kinetochores are the sites where the spindle fibers attach. Kinetochores and the spindle apparatus are responsible for the movement of the two sister chromatids to opposite poles of dividing cell nucleus during anaphase. Usually the mitosis is immediately followed by a cell division
cytokinesisCytokinesis is the process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two, to ensure that chromosome number is maintained from one generation...
. However, mitosis and cytokinesis are separate processes and can be uncoupled.
A centromere functions in sister chromatid adhesion,
kinetochoreThe kinetochore is the protein structure on chromosomes where the spindle fibers attach during division to pull the chromosomes apart....
formation, and pairing of
homologous chromosomeHomologous chromosomes are chromosomes in a biological cell that pair during cell division during the creation of gametes .Each chromosome pair contains genes for the same biological features, such as eye color, at the same locations on the chromosome.Each chromosome pair can contain the same...
s during
meiosisIn biology, meiosis is a process of reductional division in which the number of chromosomes per cell is cut in half. In animals, meiosis always results in the formation of gametes, while in other organisms it can give rise to spores. As with mitosis, before meiosis begins, the DNA in the original...
,
prophaseProphase is a stage of mitosis in which the chromatin condenses into a highly ordered structure called a chromosome in which the chromatin becomes visible. Prophase accounts for approximately 3% of the cell cycle. This process, called chromatin condensation, is mediated by the condensin complex...
and
metaphaseMetaphase, from the ancient Greek μετά and φάσις , is a stage of mitosis in the eukaryotic cell cycle in which condensed & highly coiled chromosomes, carrying genetic information, align in the middle of the cell before being separated into each of the two daughter cells...
. The centromere is also where kinetochore formation takes place: proteins bind on the centromeres that form an anchor point for the spindle formation required for the pull of chromosomes toward the centrioles during
anaphaseAnaphase, is from the ancient Greek ἀνά and φάσις , is the stage of mitosis when chromosomes separate in a eukaryotic cell. Each chromatid moves to opposite poles of the cell, the opposite ends of the mitotic spindle, near the microtubule organizing centers...
and
telophaseTelophase, from the ancient Greek "τελος" and "φασις" , is a stage in either meiosis or mitosis in an eukaryotic cell reversing the effects of prophase and prometaphase events...
of mitosis.
Improperly functioning centromeres result in the chromosomes that do not align and separate properly, resulting in
aneuploidyAneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes don't separate...
or daughter cells receiving the wrong number of chromosomes. Aneuploidy can cause conditions such as
Down syndromeDown syndrome , Down's syndrome , trisomy 21, or trisomy G is a chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British doctor who described the syndrome in 1866...
if the cells survive at all.
Centromere positions
Each chromosome has two arms, labeled p (the shorter of the two) and q (the longer). The p arm is named for "petite" meaning 'small'; the q arm is named q simply because it follows p in the alphabet. (According to the NCBI, "q" refers to the French word "queue".) They can be connected in either metacentric, submetacentric, acrocentric or telocentric manner.
Metacentric
A chromosome is
metacentric if its two arms are roughly equal in length. In some cases, a metacentric chromosome is formed by balanced
Robertsonian translocationRobertsonian translocation is a common form of chromosomal rearrangement that in humans occurs in the five acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22. Other translocations occur but do not lead to a viable foetus. They are named after the American insect geneticist W. R. B....
: the fusion of two acrocentric chromosomes to form one metacentric chromosome.
Acrocentric
If the p (short) arm is so short that is hard to observe, but still present, then the chromosome is
acrocentric (The "acro-" in acrocentric refers to the Greek word for "peak."). The
human genomeThe human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs. Twenty-two of these are autosomal chromosome pairs, while the remaining pair is sex-determining...
includes five acrocentric chromosomes:
13Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 113 million base pairs and represents between 3.5 and 4 % of the total DNA in cells....
,
14rightChromosome 14 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 14 spans about 105 million base pairs and represents between 3 and 3.5% of the total DNA in cells....
,
15right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
,
21Chromosome 21 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. The trisomy of the 21st chromosome causes Down Syndrome...
and
22Chromosome 22 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of Chromosome 22. Chromosome 22 is the second smallest human chromosome, spanning about 49 million base pairs and representing between 1.5 and 2 % of the total DNA in cells.In 1999, researchers working...
.
In an acrocentric chromosome the p arm contains genetic material including repeated sequences such as nucleolar organizing regions, and can be translocated without significant harm, as in a balanced
Robertsonian translocationRobertsonian translocation is a common form of chromosomal rearrangement that in humans occurs in the five acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22. Other translocations occur but do not lead to a viable foetus. They are named after the American insect geneticist W. R. B....
. The
domestic horseThe horse is a hoofed mammal, a subspecies of one of seven extant species of the family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
genome includes one metacentric chromosome that is
homologousIn evolutionary biology, homology refers to any similarity between characteristics of organisms that is due to their shared ancestry. The word homologous derives from the ancient Greek ομολογειν, 'to agree'. There are examples in different branches of biology...
to two acrocentric chromosomes in the
conspecificConspecificity is a concept in biology. Two or more individual organisms, populations, or taxa are termed conspecific if they belong to the same species....
but undomesticated
Przewalski's horsePrzewalski's Horse , or Dzungarian Horse, is a rare and endangered subspecies of wild horse native to the steppes of central Asia. In China, the last wild Przewalski's horses were seen in 1966...
. This may reflect either fixation of a balanced Robertsonian translocation in domestic horses or, conversely, fixation of the fission of one metacentric chromosome into two acrocentric chromosomes in Przewalski's horses. A similar situation exists between the human and great ape genomes; in this case, because more species are extant, it is apparent that the evolutionary sequence is a reduction of two acrocentric chromosomes in the great apes to one metacentric chromosome in humans (see Karyotype#Historical note).
Telocentric
A
telocentric chromosome's centromere is located at the terminal end of the chromosome. Telomeres may extend from both ends of the chromosome. For example, all mouse chromosomes are telocentric. Humans do not possess telocentric chromosomes. Some authors denote extreme acrocentric chromosomes as telocentric- 21, 22, Y.
Holocentric
With
holocentric chromosomes, the entire length of the chromosome acts as the centromere. Examples of this type of centromere can be found scattered throughout the plant and animal kingdoms with the most well known example being in the worm,
Caenorhabditis elegansCaenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
.
The centromeric sequence
There are two types of centromeres. In regional centromeres,
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information...
sequences contribute to but do not define function. Regional centromeres contain large amounts of DNA and are often packaged into
heterochromatinHeterochromatin is a tightly packed form of DNA. Its major characteristic is that transcription is limited. As such, it is a means to control gene expression, through regulation of the transcription initiation.-Structure:...
. In most eukaryotes, the centromere has no defined
DNA sequenceA DNA sequence or genetic sequence is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, with the capacity to carry information as described by the central dogma of molecular biology....
. It typically consists of large arrays of repetitive DNA (e.g. satellite DNA) where the sequence within individual repeat elements is similar but not identical. In humans, the primary centromeric repeat unit is called α-satellite (or alphoid), although a number of other sequence types are found in this region.
Point centromeres are smaller and more compact. DNA sequences are both necessary and sufficient to specify centromere identity and function in organisms with point centromeres. In budding yeasts, the centromere region is relatively small (about 125 bp DNA) and contains two highly conserved DNA sequences that serve as binding sites for essential kinetochore proteins.
Inheritance
Epigenetic inheritance plays a major role in specifying the centromere in most organisms. The daughter chromosomes will assemble centromeres in the same place as the parent chromosome, independent of sequence. However, there must still be some original way in which the centromere is specified, even if it is subsequently propagated epigenetically.
Structure
The centromeric DNA is normally in a
heterochromatinHeterochromatin is a tightly packed form of DNA. Its major characteristic is that transcription is limited. As such, it is a means to control gene expression, through regulation of the transcription initiation.-Structure:...
state, which is essential for the recruitment of the
cohesinCohesin is the protein complex responsible for binding the sister chromatids during synthesis through the G2 phase and into mitosis phase. When two sister chromatids are bound along their lengths by cohesin, the attachment is referred to as sister chromatid cohesion...
complex that mediates sister chromatid cohesion after DNA replication as well as coordinating sister chromatid separation during anaphase. In this chromatin, the normal
histoneIn biology, histones are strongly alkaline proteins found in eukaryotic cell nuclei, which package and order the DNA into structual units called nucleosomes. They are the chief protein components of chromatin, act as spools around which DNA winds, and play a role in gene regulation. Without...
H3 is replaced with a centromere-specific variant, CENP-A in humans (Lodish et al. 2004). The presence of CENP-A is believed to be important for the assembly of the kinetochore on the centromere. CENP-C has been shown to localise almost exclusively to these regions of CENP-A associated chromatin.
In the yeast
Schizosaccharomyces pombeSchizosaccharomyces pombe, also called "fission yeast", is a species of yeast. It is used 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...
(and probably in other eukaryotes), the formation of centromeric heterochromatin is connected to
RNAiRNAI 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...
. In nematodes such as
Caenorhabditis elegansCaenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
, some plants, and the insect orders Lepidoptera and Hemiptera, chromosomes are "holocentric", indicating that there is not a primary site of microtubule attachments or a primary constriction, and a "diffuse" kinetochore assembles along the entire length of the chromosome.
Centromeric aberrations
In rare cases in humans, neocentromeres can form at new sites on the chromosome. There are approximately 70 known human neocentromeres on 19 different chromosomes. The formation of a neocentromere must be coupled with or followed or proceeded by the inactivation of the centromere since chromosomes with two functional centromeres (
Dicentric chromosomeDicentric chromosome is an aberrant chromosome having two centromeres. Dicentric chromosomes form when two chromosome segments , each with a centromere, fuse end to end, with loss of their acentric fragments...
) will result in chromosome breakage during mitosis.
In some unusual cases human neocentromeres have been observed to form spontaneously on fragmented chromosomes. Some of these new positions were originally euchromatic and lack alpha satellite DNA altogether.
Centromere proteins are also the autoantigenic target for some anti-nuclear antibodies, such as
anti-centromere antibodiesAnti-centromere antibodies occur in CREST syndrome and occasionally in systemic scleroderma. They are very rare in other rheumatic conditions and in healthy persons....
.
Further reading
- Lodish et al.; Molecular Cell Biology; sixth edition 2008; ISBN 97814203142
External links