Identification of a gene at 16q24.3 that restores cellular senescence in immortal mammary tumor cells

We have mapped a cellular senescence gene, SEN16, within a genetic distance of 3-7 cM, at 16q24.3. Microcell mediated transfer of a normal human chrom osome 16, 16q22-qter or 16q23-qter restored cellular senescence in four imm ortal cell lines, derived from human and rat mammary tumors. The resumption of indefinite cell proliferation, concordant with the segregation of the d onor chromosome, confirmed the presence of a senescence gene at 16q23-qter. While microcell hybrids were maintained in selection medium to retain the donor chromosome, sporadic immortal revertant clones arose among senescent cells. Reversion to immortal growth could occur due to inactivation of the senescence gene either by a mutation or a deletion. The analysis for chromo some 16 specific DNA markers, in revertant clones of senescent microcell hy brids, revealed a consensus deletion, spanning a genetic interval of approx imately 3-7 cM at 16q24.3.