On Sep 2, 8:42 pm, Sir Frederick
fuzzysys.com> wrote:> How would you like to live 1,000,000 years?
> Quantum processes are ageless.
> ----------------------------------------------------------------------------
>
>
http://www.newscientist.com/article/dn14636-key-cancer-enzyme-gives-u...
> Key cancer enzyme gives up its secret
> 14:59 01 September 2008
>
NewScientist.com news service
> Gursharan Randhawa
> HEALTH NEWS
> Cancer milestone
>
> An enzyme linked to most human cancers has finally yielded its secrets – it may
> also help defeat ageing
> At the heart of almost all human cancers is a rogue enzyme, telomerase. Now the
> structure of a key catalytic component of the enzyme has been discovered, paving
> the way to more effective anti-cancer and, perhaps, anti-ageing drugs.
>
> Telomerase is responsible for adding unique repetitive sequences of DNA, called
> telomeres, at one end of chromosomes. These telomere caps ensure the chromosomes
> don't fall apart, but because telomerase is dormant in most adult cells each
> time a cell divides, its telomere loses a chunk of DNA. Eventually, when cells
> can no longer divide, they die – this protects against cancer.
>
> When telomerase is more active than it should be, telomeres don't get shorter.
> Instead, cells continue dividing beyond their normal limits, and become
> cancerous.
>
A telomere is a region of highly repetitive DNA at the end of a linear
chromosome that functions as a disposable buffer. Every time linear
eukaryotic chromosomes are replicated during late S-phase the DNA
polymerase complex is incapable of replicating all the way to the end
of the chromosome; if it were not for telomeres, this would quickly
result in the loss of useful genetic information, which is needed to
sustain a cell's activities. Every time a cell with linear genes
divides, it will lose a small piece of one of its strands of DNA. This
process has been referred to by James Watson and Alexei Olovnikov as
the "end replication problem" (1971).
...because of DNA replication mechanisms and because TERT expression
is repressed in many types of human cells, the telomeres of these
cells shrink a little bit every time a cell divides although in other
cellular compartments which require extensive cell division, such as
stem cells and certain white blood cells, TERT is expressed and
telomere length is maintained.
...In most multicellular eukaryotes, telomerase is only active in germ
cells. There are theories that the steady shortening of telomeres with
each replication in somatic (body) cells may have a role in senescence
and in the prevention of cancer. This is because the telomeres act as
a sort of time-delay "fuse", eventually running out after a certain
number of cell divisions and resulting in the eventual loss of vital
genetic information from the cell's chromosome with future divisions.
If telomeres become too short, they will potentially unfold from their
presumed closed structure. It is thought that the cell detects this
uncapping as DNA damage and will enter cellular senescence, growth
arrest or apoptosis depending on the cell's genetic background (p53
status). Uncapped telomeres also result in chromosomal fusions. Since
this damage cannot be repaired in normal somatic cells, the cell may
even go into apoptosis. Many aging-related diseases are linked to
shortened telomeres. Organs deteriorate as more and more of their
cells die off or enter cellular senescence.
http://en.wikipedia.org/wiki/Telemere
Are Telomeres the Key to Aging and Cancer?
http://gslc.genetics.utah.edu/features/telomeres/
> This has made telomerase a prime target for anti-cancer and anti-ageing
> therapies, but a lack of information on the structure of its catalytic subunit,
> TERT, has hindered progress.
>
> Beetle bonanza
> Emmanuel Skordalakes and his team from The Wistar Institute, Philadelphia,
> finally cracked the structure when they discovered that a gene in an insect –
> the flour beetle – could be harnessed to produce the enzyme in massive
> quantities.
>
> This enabled the team to analyse TERT using X-ray crystallography.
>
> "Structural studies of telomerase have been extremely difficult due to the size
> and complexity of the enzyme, which in turn made it difficult to isolate the
> protein component of telomerase in sufficient, stable quantities for the
> proposed studies," says Skordalakes.
>
> The structural analysis reveals that TERT (telomerase reverse transcriptase
> protein) consists of three domains, and forms a ring-like doughnut structure
> that creates a central hole. When the telomere is being built, this hole allows
> a nucleic acid template molecule about eight nucleotide bases long to fit
> inside.
>
> Anti-ageing drug?
> Previously scientists had thought that the structure of the enzyme is similar to
> HIV transcriptase and developed anti-telomerase drugs accordingly. The
> structural analysis confirms there is a similarity, but it also reveals that one
> of the domains in the TERT protein – called the carboxy-terminal extension or
> CTE – has a unique type of protein fold, never been seen before.
>
> This feature could help develop anti-telomerase drugs that specifically target
> the fold.
>
> "Now that they know what the structure of the catalytic subunit is, they can
> design drugs that can bind to the protein subunit and either inhibit its
> activity for anti-cancer treatment, or promote its activity as anti-ageing
> therapy," says Stephen Neidle, from The School of Pharmacy, University of
> London, UK.
>
> Neidle says developing drugs to target the enzyme could be used in combination
> with existing anti-telomerase anti-cancer therapies currently in clinical
> trials, such as a class of telomerase vaccines.
>
> Aubrey de Grey of the Methuselah Foundation says: "If we had a really cast-iron
> therapy against all cancers, it might well be a good idea to stimulate
> telomerase, with a drug, for example, that might have widespread anti-ageing
> effects."
>
> Journal reference: Nature (DOI:10/1038/nature07283)
>
> --
> Frederick Martin McNeill
> Poway, California, United States of America
> mmcne...@
fuzzysys.com
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> "I never cease being dumbfounded by the unbelievable things people believe."
> - Leo Rosten
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