title: Caenorhabditis elegans POT-2 telomere protein represses a mode of alternative lengthening of telomeres with normal telomere lengths.
abstract: Canonical telomere repeats at chromosome termini can be maintained by a telomerase-independent pathway termed alternative lengthening of telomeres (ALT). Human cancers that survive via ALT can exhibit long and heterogeneous telomeres, although many telomerase-negative tumors possess telomeres of normal length. Here, we report that Caenorhabditis elegans telomerase mutants that survived via ALT possessed either long or normal telomere lengths. Most ALT strains displayed end-to-end chromosome fusions, suggesting that critical telomere shortening occurred before or concomitant with ALT. ALT required the 9-1-1 DNA damage response complex and its clamp loader, HPR-17. Deficiency for the POT-2 telomere binding protein promoted ALT in telomerase mutants, overcame the requirement for the 9-1-1 complex in ALT, and promoted ALT with normal telomere lengths. We propose that telomerase-deficient human tumors with normal telomere lengths could represent a mode of ALT that is facilitated by telomere capping protein dysfunction.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Cheng
authors.forename: Ludmila
authors.initials: L
authors.lastname: Shtessel
authors.forename: Megan M
authors.initials: MM
authors.lastname: Brady
authors.forename: Shawn
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D007211:Indoles; D009154:Mutation / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D019098:Telomerase / Q000235:genetics; D059505:Telomere Homeostasis / Q000502:physiology*; D034501:Telomere-Binding Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007211:Indoles; C573833:POT-2 protein, C elegans; D034501:Telomere-Binding Proteins; C007293:DAPI; D019098:Telomerase