Open AccessA Mutation in the STN1 Gene Triggers an Alternative Lengthening of Telomere-Like Runaway Recombinational Telomere Elongation and Rapid Deletion in Yeast
Author(s) -
Shilpa Iyer,
Ashley D. Chadha,
Michael J. McEachern
Publication year - 2005
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.25.18.8064-8073.2005
Subject(s) - telomere , biology , telomere binding protein , telomerase , mutation , genetics , gene , dna repair , rad52 , crispr , dna , cas9 , rad50 , microbiology and biotechnology , rad51 , dna binding protein , transcription factor
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. InKluyveromyces lactis , we have identified a novel allele of theSTN1 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 withrad52 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 oft elomerer apidd eletion (TRD) upon reintroduction ofSTN1 . Our results suggest that the protein encoded bySTN1 , which protects the terminal 3′ telomere DNA, can regulate both ALT and TRD.