title: Dynamics of telomeres and promyelocytic leukemia nuclear bodies in a telomerase-negative human cell line.
abstract: Telomerase-negative tumor cells maintain their telomeres via an alternative lengthening of telomeres (ALT) mechanism. This process involves the association of telomeres with promyelocytic leukemia nuclear bodies (PML-NBs). Here, the mobility of both telomeres and PML-NBs as well as their interactions were studied in human U2OS osteosarcoma cells, in which the ALT pathway is active. A U2OS cell line was constructed that had lac operator repeats stably integrated adjacent to the telomeres of chromosomes 6q, 11p, and 12q. By fluorescence microscopy of autofluorescent LacI repressor bound to the lacO arrays the telomere mobility during interphase was traced and correlated with the telomere repeat length. A confined diffusion model was derived that describes telomere dynamics in the nucleus on the time scale from seconds to hours. Two telomere groups were identified that differed with respect to the nuclear space accessible to them. Furthermore, translocations of PML-NBs relative to telomeres and their complexes with telomeres were evaluated. Based on these studies, a model is proposed in which the shortening of telomeres results in an increased mobility that could facilitate the formation of complexes between telomeres and PML-NBs.
authors.affiliation: Research Group Genome Organization and Function, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Jegou
authors.forename: Inn
authors.initials: I
authors.lastname: Chung
authors.forename: Gerrit
authors.initials: G
authors.lastname: Heuvelman
authors.forename: Malte
authors.initials: M
authors.lastname: Wachsmuth
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Görisch
authors.forename: Karin M
authors.initials: KM
authors.lastname: Greulich-Bode
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
mesh_terms: D045744:Cell Line, Tumor; D002999:Clone Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D009875:Operator Regions, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D019098:Telomerase / Q000172:deficiency*; D016615:Telomere / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019098:Telomerase