Induction of cellular senescence in a telomerase negative human immortal fibroblast cell line, LCS-AF.1-3, by human chromosome 6.
In immortal cells (LCS-AF.1-3) which originated from cultured skin fibroblasts from a patient with Li-Fraumeni syndrome, a specific deletion has been identified on chromosome 6. To examine the relationship between this deletion and the loss of function in aging genes, we performed microcell mediated chromosome transfer (MMCT) of normal human chromosome 6 into LCS-AF.1-3 cells and analyzed their characteristics. Transferred human chromosome 6 induced morphological changes in the cells and cellular senescence with growth suppression. In a revertant clone that had escaped from induced senescence, a specific deletion was found at D6S309 in the transferred chromosome 6. High molecular weight telomeric sequences were lost in a clone that had been induced to senescence by introduction of human chromosome 6. On the other hand, human chromosome 7 induces senescence in immortal cells by suppressing the alternative lengthening of telomere (ALT) mechanism. We also performed MMCT of chromosome 7 and discuss the effect of chromosome transfer by comparing the two chromosomes. LCS-AF.1-3 cells containing a transferred chromosome 7 showed no changes in immortality. These results suggest that genes which are new candidates for aging and which suppress the ALT mechanism are located in the region D6S309 in human chromosome 6.
Kumata
M
M
Oral and Maxillofacial Surgery, The Nippon Dental University Hospital at Tokyo, Tokyo 102-8158, Japan.
Shimizu
M
M
Oshimura
M
M
Uchida
M
M
Tsutsui
T
T
D015139:Blotting, Southern; D016922:Cellular Senescence; D002896:Chromosomes, Human, Pair 6; D005347:Fibroblasts / Q000166:cytology* / Q000648:ultrastructure*; D017353:Gene Deletion; D005819:Genetic Markers; D005821:Genetic Techniques; D006801:Humans; D016324:Sequence Tagged Sites; D016615:Telomere / Q000648:ultrastructure; D013997:Time Factors; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D005819:Genetic Markers; D001616:beta-Galactosidase