title: Increased alternative lengthening of telomere phenotypes of telomerase-negative immortal cells upon trichostatin--a treatment.
abstract: Human immortal cells maintain their telomeres either by telomerase or by alternative lengthening of telomeres (ALT) that is based on homologous telomeric recombination. Previous studies showed that the ALT mechanism is activated in non-ALT cells when heterochromatic features are reduced. In this study, we examined the ALT phenotypes of ALT cells after treatment with trichostatin-A (TSA), which is an inhibitor of histone deacetylases and causes global chromatin decondensation. The ALT cells remained telomerase-negative after TSA treatment. ALT-associated promyelocytic leukemia (PML) nuclear bodies and telomere sister chromatid exchanges, typical ALT phenotypes, markedly increased in the TSA-treated cells, while the telomere length remained unchanged. In addition, telomerase expression in the ALT cells suppressed TSA-mediated ALT phenotype enhancement. Our results show that certain ALT phenotypes become more pronounced when chromatin is decondensed, and also suggest that the ALT mechanism may compete with telomerase for telomere maintenance in cells that lack heterochromatin.
authors.affiliation: Department of Bioscience and Biotechnology, Brain Korea 21 Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: A Ra
authors.initials: AR
authors.lastname: Jung
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Yoo
authors.forename: Yhong-Hee
authors.initials: YH
authors.lastname: Shim
authors.forename: Ye-Na
authors.initials: YN
authors.lastname: Choi
authors.forename: Hei-Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Bong-Kyeong
authors.initials: BK
authors.lastname: Oh
mesh_terms: D000107:Acetylation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010641:Phenotype; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D059505:Telomere Homeostasis
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; C509186:TERT protein, human; D019098:Telomerase