Tom Mahoney wrote:
> In article <370563F3.449D at itsa.ucsf.edu>, csoka at ITSA.UCSF.EDU says...
> > P.N.A.S. Vol. 96, Issue 7, 3723-3728, March 30, 1999
> >
> > Telomerase extends the lifespan of virus-transformed human
> > cells without net telomere lengthening
> These results would explain the very short telomeres seen in cancers with
> active telomerase.
Indeed. I must say, having read the full text, that I think Blackburn is
rather overstating the unexpectedness of this result. The "capping" effect
of telomeres -- i.e. that they protect chromosome ends from being seen as
breakages and fused end-to-end with other chromosomes -- is a long-standing
idea with much experimental evidence to support it. The culture discussed
here happened to be one whose telomerase activity was not quite sufficient
to counterbalance the rate of telomere loss during division; different
transgenes have very different levels of activity, so that is no big deal.
It is noted that "homeostasis of telomere length was eventually achieved ...
presumably by the balance between telomere synthesis by telomerase and the
erosion of telomeres during proliferation"; this says only that crisis gets
steadily worse for the cell as the chromosome shortens more and more, again
an expected result. All we are really learning from this work, as far as
I can see, is that telomerase can add telomere sequence to chromosomes that
have been shortened somewhat further than occurs in normal crisis.
It looks to me as though the authors are making a logical error, in fact.
They see average telomere length continuing to fall (for a while) in the
presence of telomerase, and I think they are inferring that telomere
repeats are not being added. They are not, in other words, allowing for
the possibility that cells are undergoing transitory telomere synthesis,
enough to stave off chromosome fusions and other aspects of crisis just
long enough to get through a division that loses all that telomere and a
bit more sub-telomere besides. This option is much more parsimonious since
it does not require telomerase to perform any function other than its known
one (the addition of TTAGGG).
In conclusion, we cannot (as far as I can see) infer that telomerase does
anything other than add TTAGGG repeats, which in turn are bound by other
proteins that perform the capping function.
Aubrey de Grey
