Alternative Telomere Lengthening
excelife at earthlink.net
Thu Sep 16 23:29:43 EST 1999
I neglected to include the cite for the attached abstract. It is; (Cancer
Res 1999 Sep 1;59(17):4175-9)
Sorry for the oversight.
In article <7rrt9s$eke$1 at oak.prod.itd.earthlink.net>, excelife at earthlink.net
>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
>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
>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
>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.
More information about the Ageing