Alternative Telomere Lengthening

Thomas Mahoney excelife at earthlink.net
Thu Sep 16 18:08:44 EST 1999


Most of the current research on immortalized cells have dealt with the 
effects of the enzyme telomerase.  But some immortalized cell lines do not 
show telomerase activity at all and are yet able to maintain telomeric 
length.

The following abstract describes how APBs, (see definition below), may be the 
factor that functions to maintain telomeric length in these cells.

Studies to determine if APBs can maintain telomeric length in normal cells 
and retain their normal phenotypical expression are currently under way.

The implications being, that this would provide an additional method of 
intervening in the aging of replicating cells, beyond those already known.

Since some cells, such as T-cells, normally have telomerase activity, this 
enzyme appears to be regulated by cellular mechanisms and the addition of 
h-TERT alone may not have the desired effect of extending the cells lines 
viable life span.  This alternative telomere maintenance system, (APBs), may 
avoid the problem of cellular regulation of telomere maintenance systems.

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Telomerase-negative immortalized human cells contain a novel type of 
promyelocytic leukemia (PML) body.

Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR

Children's Medical Research Institute, Westmead, Sydney, New South Wales, 
Australia. 


Telomerase-negative immortalized human cells maintain their telomeres by a 
mechanism known as alternative lengthening of telomeres (ALT). We report here 
that ALT cells contain a novel promyelocytic leukemia (PML) body 
(ALT-associated PML body, APB). APBs are large donut-shaped nuclear 
structures containing PML protein, telomeric DNA, and the telomere binding
proteins human telomere repeat binding factors 1 and 2. Immunostaining showed 
that APBs also contain replication factor A, RAD51, and RAD52, proteins 
involved in DNA synthesis and recombination. During immortalization, APBs 
appeared at exactly the same time as activation of ALT. APBs were found in 
ALT tumors and cell lines but not in mortal cell strains or in 
telomerase-positive cell lines or tumors.

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Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
http://home.earthlink.net/~excelife/index.html






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