Centromere
(1) Chromatid
(2) Centromere
(3) Short arm
(4) Long arm
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of mitotic spindle.
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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 DNA sequences which are in higher eukaryotes typically tandem repetitive sequences, often called "satellite DNA". 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 cytokinesis. However, mitosis and cytokinesis are separate processes and can be uncoupled.
A centromere functions in sister chromatid adhesion, kinetochore formation, and pairing of homologous chromosomes during meiosis, prophase and metaphase. 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 chromatids toward the spindle poles during anaphase and telophase of mitosis.
Improperly functioning centromeres result in the chromosomes that do not align and separate properly, resulting in aneuploidy or daughter cells receiving the wrong number of chromosomes. Aneuploidy can cause conditions such as Down syndrome if the cells survive at all. [1]
Centromere positions
Each chromosome has two arms, labeled p (the shorter of the two) and q (the longer). The p arm is named for "petit" 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" meaning 'tail'.) 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 translocation: the fusion of two acrocentric chromosomes to form one metacentric chromosome.
Submetacentric
If arms' lengths are unequal, the chromosome is said to be submetacentric
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 genome includes five acrocentric chromosomes: 13, 14, 15, 21 and 22.
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 translocation. The domestic horse genome includes one metacentric chromosome that is homologous to two acrocentric chromosomes in the conspecific but undomesticated Przewalski's horse.[2] 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. [3] 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[4] with the most well known example being in the nematode, Caenorhabditis elegans.
The centromeric sequence
There are two types of centromeres.[5] In regional centromeres, DNA sequences contribute to but do not define function. Regional centromeres contain large amounts of DNA and are often packaged into heterochromatin. In most eukaryotes, the centromere has no defined DNA sequence. 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
Since centromeric DNA sequence is not the key determinant of centromeric identity in metazoans, it is thought that epigenetic inheritance plays a major role in specifying the centromere[6]. The daughter chromosomes will assemble centromeres in the same place as the parent chromosome, independent of sequence. It has been proposed that histone H3 variant CENP-A (Centromere Protein A) is the epigenetic mark of the centromere[7]. The question arises whether there must be still some original way in which the centromere is specified, even if it is subsequently propagated epigenetically. If the centromere is inherited epigenetically from one generation to the next, the problem is pushed back to the origin of the first metazoans.
Structure
The centromeric DNA is normally in a heterochromatin state, which is essential for the recruitment of the cohesin complex that mediates sister chromatid cohesion after DNA replication as well as coordinating sister chromatid separation during anaphase. In this chromatin, the normal histone 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 human cells, the histones are found to be most enriched for H4K20me3 and H3K9me3[8] which are known heterochromatic modifications.
In the yeast Schizosaccharomyces pombe (and probably in other eukaryotes), the formation of centromeric heterochromatin is connected to RNAi.[9] In nematodes such as Caenorhabditis elegans, 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[10]. 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 chromosome) 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 antibodies.
Related links
- Monopolin
- Genetics
- Cell biology
- Chromatid
- Diploid
References
- ↑ Earnshaw WC, Ratrie H, Stetten G (June 1989). "Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads". Chromosoma 98 (1): 1–12. doi:10.1007/BF00293329. PMID 2475307.
- ↑ Myka JL, Lear TL, Houck ML, Ryder OA, Bailey E (2003). "FISH analysis comparing genome organization in the domestic horse (Equus caballus) to that of the Mongolian wild horse (E. przewalskii)". Cytogenet. Genome Res. 102 (1-4): 222–5. doi:10.1159/000075753. PMID 14970707. http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=75753&Ausgabe=229862&ProduktNr=224037.
- ↑ 5.2 KARYOTYPES, CHROMOSOMES, AND TRANSLOCATIONS
Waterston RH, Lindblad-Toh K, Birney E, et al. (December 2002). "Initial sequencing and comparative analysis of the mouse genome". Nature 420 (6915): 520–62. doi:10.1038/nature01262. PMID 12466850. - ↑ Dernburg AF (June 2001). "Here, there, and everywhere: kinetochore function on holocentric chromosomes". J. Cell Biol. 153 (6): F33–8. doi:10.1083/jcb.153.6.F33. PMID 11402076. PMC 2192025. http://www.jcb.org/cgi/pmidlookup?view=long&pmid=11402076.
- ↑ Pluta AF, Mackay AM, Ainsztein AM, Goldberg IG, Earnshaw WC (December 1995). "The centromere: hub of chromosomal activities". Science (journal) 270 (5242): 1591–4. PMID 7502067. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=7502067.
- ↑ Dalal Y., 2009, 'Epigenetic specification of centromeres', Biochem Cell Biol 2009 Feb;87(1):273-82.
- ↑ Bernad R, Sánchez P, Losada A., 2009, Epigenetic specification of centromeres by CENP-A, Exp Cell Res. 2009 Nov 15;315(19):3233-41
- ↑ Rosenfeld, Jeffrey A; Wang, Zhibin; Schones, Dustin; Zhao, Keji; DeSalle, Rob; Zhang, Michael Q (31 March 2009). "Determination of enriched histone modifications in non-genic portions of the human genome.". BMC Genomics 10 (143): 143. doi:10.1186/1471-2164-10-143. PMID 19335899.
- ↑ Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA (September 2002). "Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi". Science (journal) 297 (5588): 1833–7. doi:10.1126/science.1074973. PMID 12193640.
- ↑ Warburton PE (2004). "Chromosomal dynamics of human neocentromere formation". Chromosome Res. 12 (6): 617–26. doi:10.1023/B:CHRO.0000036585.44138.4b. PMID 15289667.
Further reading
- Lodish et al.; Molecular Cell Biology; sixth edition 2008; ISBN 97814203142
External links
- Report about Nature Genetics article that centromere of rice genome carries active genes
- Nagaki K, Cheng Z, Ouyang S, et al. (February 2004). "Sequencing of a rice centromere uncovers active genes". Nat. Genet. 36 (2): 138–45. doi:10.1038/ng1289. PMID 14716315.
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