Cloning and expression of SAG: a novel marker of cellular senescence.
Unlike immortalized cell lines, normal human fibroblasts in culture undergo replicative senescence in which the number of population doublings is limited. While fibroblasts display a variety of changes as they senesce in vitro, little is known about how gene expression varies as a function of population doubling level. We have used differential hybridization screening to identify human genes that are preferentially expressed in senescent cells. While we found several isolates that were up-regulated in late-passage cells, all appeared to be variants of the same cDNA, which we named senescence-associated gene (SAG). Our data show that SAG expression is threefold higher in senescent fibroblasts and closely parallels the progressive slowdown in growth potential, but is not cell-cycle regulated. Thus, SAG serves as an accurate marker for fibroblast growth potential during replicative senescence. Further studies demonstrated that SAG is a novel gene active in nearly all tissue types tested and that it is conserved through evolution. DNA sequencing data indicate that SAG contains a potential DNA-binding domain, suggesting that SAG may function as a regulatory protein.
Wistrom
C
C
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-2007.
Villeponteau
B
B
D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D016922:Cellular Senescence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D015854:Up-Regulation
D000199:Actins; D012333:RNA, Messenger; D004247:DNA