Jul 1, 1991

Genetic analysis of indefinite division in human cells: evidence for a cell senescence-related gene(s) on human chromosome 4

Proceedings of the National Academy of Sciences of the United States of America
Y NingO M Pereira-Smith


Earlier studies had demonstrated that fusion of normal with immortal human cells yielded hybrids having limited division potential. This indicated that the phenotype of limited proliferation (cellular senescence) is dominant and that immortal cells result from recessive changes in normal growth-regulatory genes. In additional studies, we exploited the fact that the immortal phenotype is recessive and, by fusing various immortal human cell lines with each other, identified four complementation groups for indefinite division. Assignment of cell lines to specific groups allowed us to take a focused approach to identify the chromosomes and genes involved in growth regulation that have been modified in immortal cells. We report here that introduction of a normal human chromosome 4 into three immortal cell lines (HeLa, J82, T98G) assigned to complementation group B resulted in loss of proliferation and reversal of the immortal phenotype. No effect on the proliferation potential of cell lines representative of the other complementation groups was observed. This result suggests that a gene(s) involved in cellular senescence and normal growth regulation resides on chromosome 4.

Mentioned in this Paper

Cell Aging
Genetic Analysis
Genetic Screening Method
Genetic Conditions, Dominant
Selfish DNA
Regulation of Growth
Chromosomes, Human
Genome Mapping
Chromosomes, Human, Pair 4
Group B Streptococcal Pneumonia

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