Genetic approaches to the study of replicative senescence

Genetic analyses of replicative senescence have revealed the dominance of t he senescent phenotype since whole cell fusion of normal with immortal cell s yields hybrids having limited division potential. We exploited the recess ive nature of immortality by fusing different immortal human cell lines wit h each other and identified four complementation groups For indefinite divi sion. This allowed for a focussed approach involving microcell mediated chr omosome transfer that led to the implication of chromosomes 1, 4 and 7 as l oci for cell senescence genes. More recently we have cloned the gene on chr omosome 4, MORF 4. It is a member of a family of genes with motifs suggesti ve of transcriptional regulators. Characterization of this novel gene famil y should lend Further insights into the phenomenon of replicative cell sene scence. (C) 2000 Elsevier Science Inc. All rights reserved.