How do cells count ?!

[Sigurdur Einar Vilhelmsson]

In <Pine.3.89.9501111023.A12097-0100000 at biobase.dk> thorup at BIOBASE.DK (Jan Ulrik Thorup) writes:


>Dear netters. As far as I've understood, normal tissue cells divide a 
>determined number of times (64 or so)  and then they die. Cancer cells 
>and neoplastic cell-lines seem to have lost this "limitation of number of 
>divisions" and could in theory divide indefinitely. So how do normal 
>cells count the number of divisions they have been through ? Do they 
>accumulate a "count-protein" that increases in amount/cell with 
>increasing division-passage, modify some other (more or less) vital part 
>of the cells machinery (allow DNA to be mutated, allow oxidation, allow 
>free radicals ...) slowly as they grow older or is there some other 
>mechanism. What is known about cells "counting" today ? And might that 
>"counting-meter" be reset to zero or at least be halted ?

>Sincerely,
>Jan

>E-mail thorup at biobase.dk

Hi there Jan.

	One theory on division counting in cells is connected to the telomers,
the ends of the chromosomes.  This theory was put forward by, I think, Jerry 
Shay and others, but I don´t have the references at hand.  The chromosome 
ends are packed in heterochromatin, but as the cell divides the ends shorten.
This is due to the polymerases inability to replicate the DNA on the extreme 
ends.  Studies have shown that as the chromosomes shorten, the heterochromatin
moves inwards and the theory is that this affects genes positioned close to 
the telomers.  When the heterochromatin moves into the control, or coding 
regions of these genes, they are blocked and the cell stops dividing.  
	This is, in very short, one theory of how the cells can count their
divisions.  This is all from memory, but if you want me to refresh it, or give
you references, please do not hesitate to let me know.

Sigurdur E. Vilhelmsson
sev at rhi.hi.is