Identification of a </= 600-kb region on human chromosome 1q42.3 inducing cellular senescence.
The introduction of a human chromosome 1 via microcell-mediated chromosome transfer (MMCT) induces the cellular senescence in mouse melanoma B16-F10 cells. The senescent cells maintained still the telomerase activity, which is frequently associated with immortal growth of human cells, suggesting that a telomerase-independent mechanism is involved in the senescence observed in this mouse cell line. To map the senescence-inducing gene to a specific chromosomal region, we took two experimental approaches: identification of a minimal region with the senescence-inducing activity via MMCT of a series of subchromosomal transferrable fragments (STFs), each consisting of a different profile of human chromosome 1-derived regions, and identification of a region commonly deleted from the transferred chromosome 1 in the revertant clones that escaped cellular senescence. These approaches identified a 2.7-3.0 Mb of senescence-inducing region shared among the active STFs and a 2.4-3.0 Mb of commonly deleted region in the revertant clones. These two regions overlapped each other to map the responsible gene at the 450 to 600-kb interval between UniSTS93710 and D1S3542 on chromosome 1q42.3. This study provides essential information and materials for cloning and characterization of a novel senescence-inducing gene that functions in a telomerase-independent pathway, which is likely to be conserved between mice and humans.
Yawata
Toshio
T
Department of Molecular and Cell Genetics, Faculty of Medicine, School of Life Sciences, Tottori University, Japan.
Kamino
Hiroki
H
Kugoh
Hiroyuki
H
Katoh
Motonobu
M
Nomura
Nobuo
N
Oishi
Michio
M
Horikawa
Izumi
I
Barrett
J Carl
JC
Oshimura
Mitsuo
M
D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1; D003360:Cosmids; D017353:Gene Deletion; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D016324:Sequence Tagged Sites; D019098:Telomerase / Q000235:genetics; D014407:Tumor Cells, Cultured
D019098:Telomerase