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Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids.
Oncogene. 1999 Jun 03; 18(22):3383-90.O

Abstract

Some immortalized cell lines maintain their telomeres in the absence of detectable telomerase activity by an alternative (ALT) mechanism. To study how telomere maintenance is controlled in ALT cells, we have fused an ALT cell line GM847 (SV40 immortalized human skin fibroblasts) with normal fibroblasts or with telomerase positive immortal human cell lines and have examined their proliferative potential and telomere dynamics. The telomeres in ALT cells are characteristically very heterogeneous in length, ranging from very short to very long. The ALT x normal hybrids underwent a rapid reduction in telomeric DNA and entered a senescence-like state. Immortal segregants rapidly reverted to the ALT telomere phenotype. Fusion of ALT cells to telomerase-positive immortal cells in the same immortalization complementation group resulted in hybrids that appeared immortal and also exhibited repression of the ALT telomere phenotype. In these hybrids, which were all telomerase-positive, we observed an initial rapid loss of most long telomeres, followed either by gradual loss of the remaining long telomeres at a rate similar to the rate of telomere shortening in normal telomerase-negative cells, or by maintenance of shortened telomeres. These data indicate the existence of a mechanism of rapid telomere deletion in human cells. They also demonstrate that normal cells and at least some telomerase-positive immortal cells contain repressors of the ALT telomere phenotype.

Authors+Show Affiliations

Cancer Research Group, Children's Medical Research Institute, Sydney, NSW, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10362359

Citation

Perrem, K, et al. "Repression of an Alternative Mechanism for Lengthening of Telomeres in Somatic Cell Hybrids." Oncogene, vol. 18, no. 22, 1999, pp. 3383-90.
Perrem K, Bryan TM, Englezou A, et al. Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids. Oncogene. 1999;18(22):3383-90.
Perrem, K., Bryan, T. M., Englezou, A., Hackl, T., Moy, E. L., & Reddel, R. R. (1999). Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids. Oncogene, 18(22), 3383-90.
Perrem K, et al. Repression of an Alternative Mechanism for Lengthening of Telomeres in Somatic Cell Hybrids. Oncogene. 1999 Jun 3;18(22):3383-90. PubMed PMID: 10362359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids. AU - Perrem,K, AU - Bryan,T M, AU - Englezou,A, AU - Hackl,T, AU - Moy,E L, AU - Reddel,R R, PY - 1999/6/11/pubmed PY - 1999/6/11/medline PY - 1999/6/11/entrez SP - 3383 EP - 90 JF - Oncogene JO - Oncogene VL - 18 IS - 22 N2 - Some immortalized cell lines maintain their telomeres in the absence of detectable telomerase activity by an alternative (ALT) mechanism. To study how telomere maintenance is controlled in ALT cells, we have fused an ALT cell line GM847 (SV40 immortalized human skin fibroblasts) with normal fibroblasts or with telomerase positive immortal human cell lines and have examined their proliferative potential and telomere dynamics. The telomeres in ALT cells are characteristically very heterogeneous in length, ranging from very short to very long. The ALT x normal hybrids underwent a rapid reduction in telomeric DNA and entered a senescence-like state. Immortal segregants rapidly reverted to the ALT telomere phenotype. Fusion of ALT cells to telomerase-positive immortal cells in the same immortalization complementation group resulted in hybrids that appeared immortal and also exhibited repression of the ALT telomere phenotype. In these hybrids, which were all telomerase-positive, we observed an initial rapid loss of most long telomeres, followed either by gradual loss of the remaining long telomeres at a rate similar to the rate of telomere shortening in normal telomerase-negative cells, or by maintenance of shortened telomeres. These data indicate the existence of a mechanism of rapid telomere deletion in human cells. They also demonstrate that normal cells and at least some telomerase-positive immortal cells contain repressors of the ALT telomere phenotype. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/10362359/Repression_of_an_alternative_mechanism_for_lengthening_of_telomeres_in_somatic_cell_hybrids_ L2 - http://dx.doi.org/10.1038/sj.onc.1202752 DB - PRIME DP - Unbound Medicine ER -