Open Access
PLoS Genetics, volume 9, issue 11, pages e1003931
Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination
1
Stem Cell Biology and Developmental Genetics, National Institute for Medical Research, MRC, The Ridgeway, London, United Kingdom
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Publication type: Journal Article
Publication date: 2013-11-07
Journal:
PLoS Genetics
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 4.5
ISSN: 15537390, 15537404
PubMed ID:
24244194
Cancer Research
Molecular Biology
Genetics
Ecology, Evolution, Behavior and Systematics
Genetics (clinical)
Abstract
Mammalian common fragile sites are loci of frequent chromosome breakage and putative recombination hotspots. Here, we utilized Replication Slow Zones (RSZs), a budding yeast homolog of the mammalian common fragile sites, to examine recombination activities at these loci. We found that rates of URA3 inactivation of a hisG-URA3-hisG reporter at RSZ and non-RSZ loci were comparable under all conditions tested, including those that specifically promote chromosome breakage at RSZs (hydroxyurea [HU], mec1Δ sml1Δ, and high temperature), and those that suppress it (sml1Δ and rrm3Δ). These observations indicate that RSZs are not recombination hotspots and that chromosome fragility and recombination activity can be uncoupled. Results confirmed recombinogenic effects of HU, mec1Δ sml1Δ, and rrm3Δ and identified temperature as a regulator of mitotic recombination. We also found that these conditions altered the nature of recombination outcomes, leading to a significant increase in the frequency of URA3 inactivation via loss of heterozygosity (LOH), the type of genetic alteration involved in cancer development. Further analyses revealed that the increase was likely due to down regulation of intrachromatid and intersister (IC/IS) bias in mitotic recombination, and that RSZs exhibited greater sensitivity to HU dependent loss of IC/IS bias than non RSZ loci. These observations suggest that recombinogenic conditions contribute to genome rearrangements not only by increasing the overall recombination activity, but also by altering the nature of recombination outcomes by their effects on recombination partner choice. Similarly, fragile sites may contribute to cancer more frequently than non-fragile loci due their enhanced sensitivity to certain conditions that down-regulate the IC/IS bias rather than intrinsically higher rates of recombination.
Citations by journals
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1
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Nucleus
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Nucleus
1 publication, 33.33%
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Frontiers in Microbiology
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1 publication, 33.33%
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G3: Genes, Genomes, Genetics
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G3: Genes, Genomes, Genetics
1 publication, 33.33%
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Citations by publishers
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1
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Taylor & Francis
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Taylor & Francis
1 publication, 33.33%
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 33.33%
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Genetics Society of America
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Genetics Society of America
1 publication, 33.33%
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1
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Cauwood J. D. et al. Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination // PLoS Genetics. 2013. Vol. 9. No. 11. p. e1003931.
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Cauwood J. D., Johnson A. L., Widger A., Cha R. S. Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination // PLoS Genetics. 2013. Vol. 9. No. 11. p. e1003931.
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TY - JOUR
DO - 10.1371/journal.pgen.1003931
UR - https://doi.org/10.1371%2Fjournal.pgen.1003931
TI - Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination
T2 - PLoS Genetics
AU - Cauwood, James D
AU - Johnson, Anthony L.
AU - Widger, Alexander
AU - Cha, Rita S.
PY - 2013
DA - 2013/11/07 00:00:00
PB - Public Library of Science (PLoS)
SP - e1003931
IS - 11
VL - 9
PMID - 24244194
SN - 1553-7390
SN - 1553-7404
ER -
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@article{2013_Cauwood,
author = {James D Cauwood and Anthony L. Johnson and Alexander Widger and Rita S. Cha},
title = {Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination},
journal = {PLoS Genetics},
year = {2013},
volume = {9},
publisher = {Public Library of Science (PLoS)},
month = {nov},
url = {https://doi.org/10.1371%2Fjournal.pgen.1003931},
number = {11},
pages = {e1003931},
doi = {10.1371/journal.pgen.1003931}
}
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Cauwood, James D., et al. “Recombinogenic Conditions Influence Partner Choice in Spontaneous Mitotic Recombination.” PLoS Genetics, vol. 9, no. 11, Nov. 2013, p. e1003931. https://doi.org/10.1371%2Fjournal.pgen.1003931.