Alternative Telomere Lengthening
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
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.
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,
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.
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
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