Re: Telomeres, mutation rates and "breakthroughs"

From: Damien Broderick (d.broderick@english.unimelb.edu.au)
Date: Sun May 07 2000 - 07:50:36 MDT


Phil says:

>Is it possible that one of the reasons for the apparent extended
>youthfulness, etc., exhibited in the recent calve clones or some of the cell
>culture experiments is due to the fact that the stable environment, with
>only cells of the same kind present, made for a much stronger reinforcement
>signal pattern to the cells of each generation? ...
>Thus, the normal correction procedures that keep a cell on track might use
>that unambiguous signal as a referent, and actually clean up a lot of
>accumulated error.

I rather doubt it, since this felicitous and constrained in vitro
environment should also benefit all the classic cell experiments that hit
their usual Hayflick limit. This lot did way better.

Robert Bradbury raised the question earlier in this thread as to whether
the telomerase gene goes inappropriately active before or after the
accidents to genetic brakes and accelerators that permit cells to go
cancerous. My guess is that most often it's switched onprior to the other
events (by chance accident, not as part of a designed sequence). Turning on
runaway growth factors and switching off inhibitors and apoptotic systems
etc (again by chance) will get a tumor started, but telomere erosion will
stop it fairly soon. If the tumor mass is comparatively small, and the
number of remaining normal cell divisions only 50 or fewer, there's not all
that much opportunity for a chance mutation to activate a dormant
telomerase gene in the cell clone. But switch it on early and the immortal
cell clone can accumulate mutations for as long as takes to gather the
other four or five master-code errors needed to make it into a monster.

I have no empirical evidence for this assessment, however.

Damien



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