Identification of a </= 600-kb region on human chromosome 1q42.3 inducing cellular senescence

Oncogene. 2003 Jan 16;22(2):281-90. doi: 10.1038/sj.onc.1206143.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellular Senescence / physiology*
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 1*
  • Cosmids
  • Gene Deletion
  • Humans
  • Melanoma / genetics
  • Melanoma / pathology
  • Mice
  • Sequence Tagged Sites
  • Telomerase / genetics
  • Tumor Cells, Cultured


  • Telomerase