MOLECULAR ORGANISATION OF CENTROMERE AND TELOMERE
Recently (In 1997), proteins have been isolated
from telomerase in yeast and a ciliated protozoan (Euplotes) which could be the RT component of telomerase. These were
p123 in Euplotes and Est2 in
yeast. In recent years, efforts have also been made to understand, how the
telomere length is monitored in telomerase, because uncontrolled activity of
telomerase will lead to indefinite elongation of telomeres. Proteins binding to
telomere repeats have been identified, which block the elongation of telomeres.
These include rap1p in budding
yeast, Taz1p in fission yeast and TRF in humans. The significance of
these proteins lies in the following two observations made in recent years: (i)
Shortening of telomere tract (repeat sequence) is associated with senescence
and aging; (ii) Controlled elongation of telomere is an essential step in
tumour formation and oncogenesis. However, even in tumour cells, this telomere
length does not increase in an uncontrolled manner, and the elongation is regulated.
However, we still do not know, ‘how does the cell measure the telomere length,
and how is this information used to regulate the length of telomeres’?
Centromere
As earlier described,
centromere is a unique region of a chromosome characterized by a constriction,
where the two chromatids remain joined together after chromosome replication.
On each of these centromeres, specialized DNA-protein complexes known as
kinetochores assemble. Each chromosome has two kinetochores, one on each sister
chromatid, facing in opposite directions. These kinetochores are the sites for
binding of kinetochore microtubules
(spindle), which assist in the movement of chromosomes during anaphase.
The DNA sequence
representing the centromere contain the information specifying the assembly of
kinetochore. These centromeric DNA sequences have been isolated and
characterized in a number of organisms but, unlike the telomeric sequences,
have not been found to be conserved. 
Telomere
The sequences at the ends of eukaryotic
chromosomes, called telomeres, play critical roles in chromosome replication
and maintenance. Telomeres were initially recognized as distinct structures
because broken chromosomes were highly unstable in eukaryotic cells, implying
that specific sequences are required at normal chromosomal termini.
In recent years the structure of telomeres in a wide variety of
organisms has been studied to demonstrate that telomeres are highly conserved
elements throughout the eukaryotes, both in structure and function. Telomeric
DNA has been shown to consist of simple randomly repeated sequences,
characterized by clusters of G residues in one strand
and C residues in the other. Another feature is a 3’ overhang (12-16
nucleotides in length) of the G-rich strand. For example, the
sequence of telomere repeats in humans and other mammals is AGGGTT, and the
telomere repeat in Tetrahymena is GGGGTT.
These sequences are repeated hundreds or
thousands of times, thus spanning up to several kilobases, and terminate with
an overhang of single-stranded DNA. Recent results suggest that the repeated
sequences of telomere DNA form loops at the ends of chromosomes, thereby
protecting the chromosome termini from degradation .Telomeres play a critical
role in replication of the ends of linear DNA molecules.
The same repeated sequence
is found at the ends of all chromosomes in a species and the same telomere
sequence may occur in widely divergent species, such as humans, some acellular
slime molds (trypanosome) and the
fungi like Neurospora. At every
telomere, as much as 10 kilobase of this repeat sequence may occur. The
telomric DNA is also complexed with non-histone proteins,the complex structure
being associated with nuclear lamina, as shown in Oxytricha, a ciliated protozoan. The telomeric DNA is synthesized
under the influence of telomerase.
An enzyme which has been shown to be a ribonucleoprotien, whose RNA component
works as a template for synthesis of telomeric DNA repeats and protein
component has reverse transcriptase (RT) activity.
Comments
Post a Comment