| First Author | Liu Y | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 6 | Pages | 3597-602 |
| PubMed ID | 11904422 | Mgi Jnum | J:267119 |
| Mgi Id | MGI:6258969 | Doi | 10.1073/pnas.062549199 |
| Citation | Liu Y, et al. (2002) Preferential maintenance of critically short telomeres in mammalian cells heterozygous for mTert. Proc Natl Acad Sci U S A 99(6):3597-602 |
| abstractText | Prolonged growth of murine embryonic stem (ES) cells lacking the telomerase reverse transcriptase, mTert, results in a loss of telomere DNA and an increased incidence of end-to-end fusions and aneuploidy. Furthermore, loss of only one copy of mTert also results in telomere shortening intermediate between wild-type (wt) and mTert-null ES cells [Liu, Y., Snow, B. E., Hande, M. P., Yeung, D., Erdmann, N. J., Wakeham, A., Itie, A., Siderovski, D. P., Lansdorp, P. M., Robinson, M. O. & Harrington, L. (2000) Curr. Biol. 10, 1459-1462]. Unexpectedly, although average telomere length in mTert(+/-) ES cells declined to a similar level as mTert-null ES cells, mTert(+/-) ES cell lines retained a minimal telomeric DNA signal at all chromosome ends. Consequently, no end-to-end fusions and genome instability were observed in the latest passages of mTert(+/-) ES cell lines. These data uncover a functional distinction between the dosage-dependent function of telomerase in average telomere-length maintenance and the selective maintenance of critically short telomeres in cells heterozygous for mTert. In normal and tumor cells, we suggest that telomerase activity insufficient to maintain a given average telomere length may, nonetheless, provide a protective advantage from end-to-end fusion and genome instability. |
