Open Access
Proceedings of the National Academy of Sciences of the United States of America, volume 110, issue 49, pages 19866-19871
Genome rearrangements caused by interstitial telomeric sequences in yeast
Aksenova Anna Y
1
,
Greenwell Patricia W
2
,
Dominska Margaret
2
,
Shishkin Alexander A
1
,
Kim Jane C
1
,
Petes Thomas D.
2
,
Mirkin Sergei M.
1
1
Department of Biology, Tufts University, Medford, MA 02155; and
|
2
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
Publication type: Journal Article
Publication date: 2013-11-04
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 11.1
ISSN: 00278424, 10916490
PubMed ID:
24191060
Multidisciplinary
Abstract
Significance Telomeres are composed of simple repetitive DNA sequences that normally are located at the ends of the chromosomes. Occasionally, however, they also are found inside chromosomes. Some of these internal or interstitial telomeric sequences colocalize with chromosomal fragile sites, preferred sites of breakage in some cancers and hereditary human diseases. The mechanisms responsible for genome instability at interstitial telomeric sequences are unclear. We developed a system to study genetic instabilities caused by these sequences in a model organism (baker’s yeast) that allowed us to characterize various chromosomal rearrangements and to measure the likelihood of their formation. We found that interstitial telomeric sequences promote the formation of deletions, duplications, inversions, and translocations, and we proposed molecular mechanisms responsible for these events. Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an intron of a reporter gene inside a yeast chromosome. We observed a very high rate of small insertions and deletions within the repeats. We also found frequent gross chromosome rearrangements, including deletions, duplications, inversions, translocations, and formation of acentric minichromosomes. The inversions are a unique class of chromosome rearrangement involving an interaction between the ITS and the true telomere of the chromosome. Because we previously found that Ytel repeats cause strong replication fork stalling, we suggest that formation of double-stranded DNA breaks within the Ytel sequences might be responsible for these gross chromosome rearrangements.
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- We do not take into account publications that without a DOI.
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Aksenova A. Y. et al. Genome rearrangements caused by interstitial telomeric sequences in yeast // Proceedings of the National Academy of Sciences of the United States of America. 2013. Vol. 110. No. 49. pp. 19866-19871.
GOST all authors (up to 50)
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Aksenova A. Y., Greenwell P. W., Dominska M., Shishkin A. A., Kim J. C., Petes T. D., Mirkin S. M. Genome rearrangements caused by interstitial telomeric sequences in yeast // Proceedings of the National Academy of Sciences of the United States of America. 2013. Vol. 110. No. 49. pp. 19866-19871.
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TY - JOUR
DO - 10.1073/pnas.1319313110
UR - https://doi.org/10.1073%2Fpnas.1319313110
TI - Genome rearrangements caused by interstitial telomeric sequences in yeast
T2 - Proceedings of the National Academy of Sciences of the United States of America
AU - Aksenova, Anna Y
AU - Greenwell, Patricia W
AU - Dominska, Margaret
AU - Shishkin, Alexander A
AU - Kim, Jane C
AU - Petes, Thomas D.
AU - Mirkin, Sergei M.
PY - 2013
DA - 2013/11/04 00:00:00
PB - Proceedings of the National Academy of Sciences (PNAS)
SP - 19866-19871
IS - 49
VL - 110
PMID - 24191060
SN - 0027-8424
SN - 1091-6490
ER -
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@article{2013_Aksenova,
author = {Anna Y Aksenova and Patricia W Greenwell and Margaret Dominska and Alexander A Shishkin and Jane C Kim and Thomas D. Petes and Sergei M. Mirkin},
title = {Genome rearrangements caused by interstitial telomeric sequences in yeast},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2013},
volume = {110},
publisher = {Proceedings of the National Academy of Sciences (PNAS)},
month = {nov},
url = {https://doi.org/10.1073%2Fpnas.1319313110},
number = {49},
pages = {19866--19871},
doi = {10.1073/pnas.1319313110}
}
Cite this
MLA
Copy
Aksenova, Anna Y., et al. “Genome rearrangements caused by interstitial telomeric sequences in yeast.” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 49, Nov. 2013, pp. 19866-19871. https://doi.org/10.1073%2Fpnas.1319313110.