A mutation in the STN1 gene triggers an alternative lengthening of telomere-like runaway recombinational telomere elongation and rapid deletion in yeast.
Some human cancer cells achieve immortalization by using a recombinational mechanism termed ALT (alternative lengthening of telomeres). A characteristic feature of ALT cells is the presence of extremely long and heterogeneous telomeres. The molecular mechanism triggering and maintaining this pathway is currently unknown. In Kluyveromyces lactis, we have identified a novel allele of the STN1 gene that produces a runaway ALT-like telomeric phenotype by recombination despite the presence of an active telomerase pathway. Additionally, stn1-M1 cells are synthetically lethal in combination with rad52 and display chronic growth and telomere capping defects including extensive 3' single-stranded telomere DNA and highly elevated subtelomere gene conversion. Strikingly, stn1-M1 cells undergo a very high rate of telomere rapid deletion (TRD) upon reintroduction of STN1. Our results suggest that the protein encoded by STN1, which protects the terminal 3' telomere DNA, can regulate both ALT and TRD.
Iyer
Shilpa
S
Department of Genetics, Fred C. Davison Life Science Complex, University of Georgia, Athens, GA 30602, USA.
Chadha
Ashley D
AD
McEachern
Michael J
MJ
D000595:Amino Acid Sequence; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D007716:Kluyveromyces / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic; D017384:Sequence Deletion / Q000235:genetics; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics*
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D051721:Rad52 DNA Repair and Recombination Protein; D034501:Telomere-Binding Proteins; D019098:Telomerase