Genetic approaches to the study of replicative senescence.

Genetic analyses of replicative senescence have revealed the dominance of the senescent phenotype since whole cell fusion of normal with immortal cells yields hybrids having limited division potential. We exploited the recessive nature of immortality by fusing different immortal human cell lines with each other and identified four complementation groups for indefinite division. This allowed for a focussed approach involving microcell mediated chromosome transfer that led to the implication of chromosomes 1, 4 and 7 as loci for cell senescence genes. More recently we have cloned the gene on chromosome 4, MORF 4. It is a member of a family of genes with motifs suggestive of transcriptional regulators. Characterization of this novel gene family should lend further insights into the phenomenon of replicative cell senescence.