Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells.
The Werner syndrome (WS) is characterized by the premature onset and accelerated rate of development of major geriatric disorders, including atherosclerosis, diabetes mellitus, osteoporosis, ocular cataracts, and various neoplasms. Cultures of WS skin-fibroblastlike cells have been previously shown to undergo accelerated rates of decline of the replicative potentials and to exhibit variegated chromosomal translocations and deletions. Since the replicative decline of normal somatic cells is associated with a loss of telomeric repeats, we investigated the kinetics of telomeric repeat loss in WS cells. The mean length of telomere restriction fragments (TRF) from the earliest passages of WS cells studied was not shorter than those of controls, possibly reflecting selective pressure for subsets of cells with relatively high residual replicative capacity. Statistical evidence indicated an accelerated shortening of TRF length in serially passaged WS cultures, but the mean TRF lengths of WS cultures that had ceased replicating were significantly longer than those of senescent controls. Thus, while accelerated loss of telomeric repeats could potentially explain the rapid decline in proliferation of WS cells, it is possible that WS cells exit the cell cycle via mechanisms that differ from those of replicatively senescent cells from control subjects.
Schulz
V P
VP
Fred Hutchinson Cancer Research Institute, Seattle WA 98195, USA.
Zakian
V A
VA
Ogburn
C E
CE
McKay
J
J
Jarzebowicz
A A
AA
Edland
S D
SD
Martin
G M
GM
D000328:Adult; D002455:Cell Division; D002478:Cells, Cultured; D002872:Chromosome Deletion; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012867:Skin; D016615:Telomere / Q000235:genetics*; D014898:Werner Syndrome / Q000235:genetics* / Q000473:pathology
D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases; C040158:GTAC-specific type II deoxyribonucleases