title: Organismal propagation in the absence of a functional telomerase pathway in Caenorhabditis elegans.
abstract: To counteract replication-dependent telomere shortening most eukaryotic cells rely on the telomerase pathway, which is crucial for the maintenance of proliferative potential of germ and stem cell populations of multicellular organisms. Likewise, cancer cells usually engage the telomerase pathway for telomere maintenance to gain immortality. However, in ∼10% of human cancers telomeres are maintained through telomerase-independent alternative lengthening of telomeres (ALT) pathways. Here, we describe the generation and characterization of C. elegans survivors in a strain lacking the catalytic subunit of telomerase and the nematode telomere-binding protein CeOB2. These clonal strains, some of which have been propagated for >180 generations, represent the first example of a multicellular organism with canonical telomeres that can survive without a functional telomerase pathway. The animals display the heterogeneous telomere length characteristic for ALT cells, contain single-stranded C-circles, a transcription profile pointing towards an adaptation to chronic stress and are therefore a unique and valuable tool to decipher the ALT mechanism.
authors.affiliation: Molecular and Cellular Biology Department, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lackner
authors.forename: Marcela
authors.initials: M
authors.lastname: Raices
authors.forename: Hugo
authors.initials: H
authors.lastname: Maruyama
authors.forename: Candy
authors.initials: C
authors.lastname: Haggblom
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D016019:Survival Analysis; D019098:Telomerase / Q000172:deficiency*; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000172:deficiency*
chemical_list: D034501:Telomere-Binding Proteins; D019098:Telomerase