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Molecular and Cellular Biology, June 2005, p. 4406-4412, Vol. 25, No. 11
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.11.4406-4412.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Recombination at Long Mutant Telomeres Produces Tiny Single- and Double-Stranded Telomeric Circles

Cindy Groff-Vindman,¹ Anthony J. Cesare,² Shobhana Natarajan,^1, Jack D. Griffith,² and Michael J. McEachern^1*

Department of Genetics, University of Georgia, Life Sciences Bldg., Rm. C320, Athens, Georgia 30602,¹ Lineberger Comprehensive Cancer Center, Rm. 11-119, CB 7295, Mason Farm Rd., University of North Carolina, Chapel Hill, North Carolina 27599-7295²

Received 6 January 2005/ Returned for modification 2 February 2005/ Accepted 7 March 2005

Recombinational telomere elongation (RTE) known as alternate lengthening of telomeres is the mechanism of telomere maintenance in up to 5 to 10% of human cancers. The telomeres of yeast mutants lacking telomerase can also be maintained by recombination. Previously, we proposed the roll-and-spread model to explain this elongation in the yeast Kluveromyces lactis. This model suggests that a very small (100-bp) circular molecule of telomeric DNA is copied by a rolling circle event to generate a single long telomere. The sequence of this primary elongated telomere is then spread by recombination to all remaining telomeres. Here we show by two-dimensional gel analysis and electron microscopy that small circles of single- and double-stranded telomeric DNA are commonly made by recombination in a K. lactis mutant with long telomeres. These circles were found to be especially abundant between 100 and 400 bp (or nucleotides). Interestingly, the single-stranded circles consist of only the G-rich telomeric strand sequence. To our knowledge this is the first report of single-stranded telomeric circles as a product of telomere dysfunction. We propose that the small telomeric circles form through the resolution of an intratelomeric strand invasion which resembles a t-loop. Our data reported here demonstrate that K. lactis can, in at least some circumstances, make telomeric circles of the very small sizes predicted by the roll-and-spread model. The very small circles seen here are both predicted products of telomere rapid deletion, a process observed in both human and yeast cells, and predicted templates for roll-and-spread RTE.

Present address: University of Texas Southwestern Medical Center, Dallas, TX 75390.

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