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Molecular and Cellular Biology, September 2005, p. 8064-8073, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8064-8073.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Mutation in the STN1 Gene Triggers an Alternative Lengthening of Telomere-Like Runaway Recombinational Telomere Elongation and Rapid Deletion in Yeast

Shilpa Iyer, Ashley D. Chadha,{dagger} and Michael J. McEachern*

Department of Genetics, Fred C. Davison Life Science Complex, University of Georgia, Athens, Georgia 30602

Received 13 April 2005/ Returned for modification 13 May 2005/ Accepted 11 July 2005

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.

* Corresponding author. Mailing address: Department of Genetics, Fred C. Davison Life Science Complex, University of Georgia, Athens, GA 30602. Phone: (706) 542-1821. Fax: (706) 542-3910. E-mail: mjm{at}uga.edu.

{dagger} Present address: Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-0004.

Molecular and Cellular Biology, September 2005, p. 8064-8073, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8064-8073.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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