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Human chromosome 5 carries a putative telomerase repressor gene
Hiroyuki Kugoh1, Katsuyo Shigenami, Kenji Funaki
1Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University, Japan.
Genes, Chromosomes & Cancer
|December 4, 2002
Summary
Human chromosome 5 contains genes that repress telomerase activity. Loss of these genes on chromosome 5 leads to telomerase reactivation in cancer cells, suggesting a role in tumor development.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Telomerase is active in germ cells, stem cells, and most tumors, but repressed in normal somatic cells.
- This suggests the presence of regulatory factors that suppress telomerase activity in healthy cells.
Purpose of the Study:
- To identify human chromosomes carrying genes that repress telomerase activity.
- To investigate the role of these genes in telomerase reactivation in cancer cells.
Main Methods:
- Utilized microcell fusion to create hybrid cell lines (B16-F10) containing individual human chromosomes.
- Analyzed telomerase activity and mTERT mRNA levels in hybrid cells.
- Mapped the telomerase repressor gene using functional analysis and deletion mapping of revertant clones.
Main Results:
- Introduction of human chromosome 5 into B16-F10 cells inhibited telomerase activity.
- Reactivation of telomerase correlated with deletion/rearrangement of chromosome 5.
- Suppression of telomerase activity was linked to reduced mTERT mRNA levels.
- A telomerase repressor gene was mapped to human chromosome bands 5p11-p13.
Conclusions:
- Human chromosome 5 harbors gene(s) that regulate mTERT expression and repress telomerase activity.
- Loss of these genes on chromosome 5 can lead to telomerase reactivation, a common event in cancer.