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High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events

In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events...

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Autores principales: St. Charles, Jordan, Hazkani-Covo, Einat, Yin, Yi, Andersen, Sabrina L., Dietrich, Fred S., Greenwell, Patricia W., Malc, Ewa, Mieczkowski, Piotr, Petes, Thomas D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316642/
https://www.ncbi.nlm.nih.gov/pubmed/22267500
http://dx.doi.org/10.1534/genetics.111.137927
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author St. Charles, Jordan
Hazkani-Covo, Einat
Yin, Yi
Andersen, Sabrina L.
Dietrich, Fred S.
Greenwell, Patricia W.
Malc, Ewa
Mieczkowski, Piotr
Petes, Thomas D.
author_facet St. Charles, Jordan
Hazkani-Covo, Einat
Yin, Yi
Andersen, Sabrina L.
Dietrich, Fred S.
Greenwell, Patricia W.
Malc, Ewa
Mieczkowski, Piotr
Petes, Thomas D.
author_sort St. Charles, Jordan
collection PubMed
description In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either γ-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and γ-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by γ-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote.
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spelling pubmed-33166422012-04-06 High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events St. Charles, Jordan Hazkani-Covo, Einat Yin, Yi Andersen, Sabrina L. Dietrich, Fred S. Greenwell, Patricia W. Malc, Ewa Mieczkowski, Piotr Petes, Thomas D. Genetics Investigations In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either γ-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and γ-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by γ-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote. Genetics Society of America 2012-04 /pmc/articles/PMC3316642/ /pubmed/22267500 http://dx.doi.org/10.1534/genetics.111.137927 Text en Copyright © 2012 by the Genetics Society of America Available freely online through the author-supported open access option.
spellingShingle Investigations
St. Charles, Jordan
Hazkani-Covo, Einat
Yin, Yi
Andersen, Sabrina L.
Dietrich, Fred S.
Greenwell, Patricia W.
Malc, Ewa
Mieczkowski, Piotr
Petes, Thomas D.
High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events
title High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events
title_full High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events
title_fullStr High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events
title_full_unstemmed High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events
title_short High-Resolution Genome-Wide Analysis of Irradiated (UV and γ-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events
title_sort high-resolution genome-wide analysis of irradiated (uv and γ-rays) diploid yeast cells reveals a high frequency of genomic loss of heterozygosity (loh) events
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316642/
https://www.ncbi.nlm.nih.gov/pubmed/22267500
http://dx.doi.org/10.1534/genetics.111.137927
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