title: The role of nonhomologous end-joining components in telomere metabolism in Kluyveromyces lactis.
abstract: The relationship between telomeres and nonhomologous end-joining (NHEJ) is paradoxical, as NHEJ proteins are part of the telomere cap, which serves to differentiate telomeres from DNA double-strand breaks. We explored these contradictory functions for NHEJ proteins by investigating their role in Kluyveromyces lactis telomere metabolism. The ter1-4LBsr allele of the TER1 gene resulted in the introduction of sequence altered telomeric repeats and subsequent telomere-telomere fusions (T-TFs). In this background, Lig4 and Ku80 were necessary for T-TFs to form. Nej1, essential for NHEJ at internal positions, was not. Hence, T-TF formation was mediated by an unusual NHEJ mechanism. Rad50 and mre11 strains exhibited stable short telomeres, suggesting that Rad50 and Mre11 were required for telomerase recruitment. Introduction of the ter1-4LBsr allele into these strains failed to result in telomere elongation as normally observed with the ter1-4LBsr allele. Thus, the role of Rad50 and Mre11 in the formation of T-TFs was unclear. Furthermore, rad50 and mre11 mutants had highly increased subtelomeric recombination rates, while ku80 and lig4 mutants displayed moderate increases. Ku80 mutant strains also contained extended single-stranded 3' telomeric overhangs. We concluded that NHEJ proteins have multiple roles at telomeres, mediating fusions of mutant telomeres and ensuring end protection of normal telomeres.
authors.affiliation: Department of Developmental Biology/Wenner-gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Sidney D
authors.initials: SD
authors.lastname: Carter
authors.forename: Shilpa
authors.initials: S
authors.lastname: Iyer
authors.forename: Jianing
authors.initials: J
authors.lastname: Xu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McEachern
authors.forename: Stefan U
authors.initials: SU
authors.lastname: Aström
mesh_terms: D011088:DNA Ligases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D007716:Kluyveromyces / Q000235:genetics / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D009841:Oligonucleotides; D034501:Telomere-Binding Proteins; D011088:DNA Ligases