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In this article we will discuss about the molecular structure of centromere.
Eukaryotic chromosomes possess a segregational device called centromere which is responsible for the chromosomc movement during cell division. Chromosome fragments without a centromere (acentric fragments) are unable to move to any of the poles during cell division; as a result, they are excluded from the daughter nuclei and remain in the cytoplasm where they are degraded.
The centromeric region contains a disk-shaped structure of about 200 nm in diameter which is the site for microtubule attachment; this structure is called kinetochore. The kinetochore functions as the “microtubule organizing centre” (MTOC) of the chromosome. Such centios also occur at the poles, in the vicinity of centriole.
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A single microtubule is sufficient to move a chromosome. However, the number of microtubules attached to a single chromosome vary from one to many in the different species. In yeast and some other species, there is only one microtubule per kinetochore, but in human, 20 to 40 microtubules are found attached to one kinetochore.
The centromere is surrounded by heterochromatin that can be observed by the C-banding technique. Satellite DNA sequences are located on both the sides of centromeres. The minimum region of a chromosome necessary for centromeric function is called a CEN fragment or CEN region. In case of yeast, some plasmids have been produced using genetic engineering. But these plasmids are unstable and are lost during mitosis and meiosis.
When a CEN fragment is inserted in such an unstable plasmid, the plasmid becomes stable. Each of the 17 chromosomes of yeast contains a different centromeric sequence, each sequence being with in 120 bp in length.
However, all the sequences contain substantial regions of homology, and can be inverted or swapped from one chromosome to another without loss of function. The yeast centromeric DNA contains three distinguishable sequences (Fig. 8.8).
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(i) Conserved element I (CDE I):
It is composed of 9 bp and is located at the left end of the centromere; it shows minor variations.
(ii) Conserved element II (CDE II):
This element is the middle region containing 80-90 bp. A=T rich sequences constitute more than 90% of this region.
(iii) Conserved element III (CDE III):
This element consists of 11 bp and is located at the right end of the centromere (Fig. 8.8). It is a highly conserved sequence.
Point mutations in the CCG sequence of the conserved element III leads to an inactivation of the centromeric function. Mutations in the other elements, however, cause only a reduction in the centromeric function. Certain proteins or protein complexes bind to specific regions of the CEN sequences.
Protein CBF-I binds to CDEI element. Proteins CBF-IIIA, CBF-IIIB and CBF-IIIC from a complex (M.W. 2.4 × 105 Daltons) which binds to the CDE-III region. This protein complex has some motor activity due to which the centromeric region of the chromosome becomes attached to microtubules. Mitotic chromosome movement is inhibited when mutation occurs in the genes coding for CBF-III proteins.
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The yeast centromeric sequences bind to specific proteins which initiate to form a kinetochore (multi-protein complex). The kinetochore, in turn, binds to the end of a single microtubule. Mammalian centromeres are thought to contain different and much longer DNA sequences. They form larger kinetochores each of which binds to several microtubules.
