The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae

Shay Ben-Aroya; Piotr A. Mieczkowski; Thomas D. Petes; Martin Kupiec

doi:10.1016/j.molcel.2004.06.002

The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae

Shay Ben-Aroya, Piotr A. Mieczkowski, Thomas D. Petes, Martin Kupiec

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the main family of dispersed repeats in Saccharomyces cerevisiae, exhibit low levels of exchange. Other regions in the genome have relatively high rates of meiotic recombination (hotspots). We show that a Ty element adjacent to the HIS4 recombination hotspot substantially reduces its activity, eliminating local DSB formation. We demonstrate that the Ty has a closed (nuclease-insensitive) chromatin configuration that is also imposed on the flanking DNA sequences. The compact chromatin structure is determined by sequences at the N terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores both open chromatin conformation and DSB formation. The chromatin configuration of Ty elements precludes initiation of recombination, thus preventing potentially lethal exchanges between repeated sequences.

Original language	English
Pages (from-to)	221-231
Number of pages	11
Journal	Molecular Cell
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2004.06.002
State	Published - 23 Jul 2004
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to Carol Wu and Michael Lichten for advice on DNase I assays. We thank all members of the Kupiec lab for encouragement and support, and Yael Aylon for critical comments on the manuscript. This work was supported by a grant to M.K. and T.P. by the USA-Israel Bi-national Fund, by a grant to M.K. from the Israel Science Foundaton, and by an NIH grant to T.P. (GM24110). S.B.-A. was supported by travel grants from the Constantiner Institute for Molecular Genetics.

Funding

We are grateful to Carol Wu and Michael Lichten for advice on DNase I assays. We thank all members of the Kupiec lab for encouragement and support, and Yael Aylon for critical comments on the manuscript. This work was supported by a grant to M.K. and T.P. by the USA-Israel Bi-national Fund, by a grant to M.K. from the Israel Science Foundaton, and by an NIH grant to T.P. (GM24110). S.B.-A. was supported by travel grants from the Constantiner Institute for Molecular Genetics.

Funders	Funder number
Constantiner Institute for Molecular Genetics
USA-Israel Bi-national Fund
National Institutes of Health
National Institute of General Medical Sciences	R01GM024110
Israel Science Foundation

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10.1016/j.molcel.2004.06.002

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title = "The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae",

abstract = "Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the main family of dispersed repeats in Saccharomyces cerevisiae, exhibit low levels of exchange. Other regions in the genome have relatively high rates of meiotic recombination (hotspots). We show that a Ty element adjacent to the HIS4 recombination hotspot substantially reduces its activity, eliminating local DSB formation. We demonstrate that the Ty has a closed (nuclease-insensitive) chromatin configuration that is also imposed on the flanking DNA sequences. The compact chromatin structure is determined by sequences at the N terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores both open chromatin conformation and DSB formation. The chromatin configuration of Ty elements precludes initiation of recombination, thus preventing potentially lethal exchanges between repeated sequences.",

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note = "Funding Information: We are grateful to Carol Wu and Michael Lichten for advice on DNase I assays. We thank all members of the Kupiec lab for encouragement and support, and Yael Aylon for critical comments on the manuscript. This work was supported by a grant to M.K. and T.P. by the USA-Israel Bi-national Fund, by a grant to M.K. from the Israel Science Foundaton, and by an NIH grant to T.P. (GM24110). S.B.-A. was supported by travel grants from the Constantiner Institute for Molecular Genetics.",

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AU - Petes, Thomas D.

AU - Kupiec, Martin

N1 - Funding Information: We are grateful to Carol Wu and Michael Lichten for advice on DNase I assays. We thank all members of the Kupiec lab for encouragement and support, and Yael Aylon for critical comments on the manuscript. This work was supported by a grant to M.K. and T.P. by the USA-Israel Bi-national Fund, by a grant to M.K. from the Israel Science Foundaton, and by an NIH grant to T.P. (GM24110). S.B.-A. was supported by travel grants from the Constantiner Institute for Molecular Genetics.

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N2 - Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the main family of dispersed repeats in Saccharomyces cerevisiae, exhibit low levels of exchange. Other regions in the genome have relatively high rates of meiotic recombination (hotspots). We show that a Ty element adjacent to the HIS4 recombination hotspot substantially reduces its activity, eliminating local DSB formation. We demonstrate that the Ty has a closed (nuclease-insensitive) chromatin configuration that is also imposed on the flanking DNA sequences. The compact chromatin structure is determined by sequences at the N terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores both open chromatin conformation and DSB formation. The chromatin configuration of Ty elements precludes initiation of recombination, thus preventing potentially lethal exchanges between repeated sequences.

AB - Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the main family of dispersed repeats in Saccharomyces cerevisiae, exhibit low levels of exchange. Other regions in the genome have relatively high rates of meiotic recombination (hotspots). We show that a Ty element adjacent to the HIS4 recombination hotspot substantially reduces its activity, eliminating local DSB formation. We demonstrate that the Ty has a closed (nuclease-insensitive) chromatin configuration that is also imposed on the flanking DNA sequences. The compact chromatin structure is determined by sequences at the N terminus of the Ty. Increased binding of the Rap1 protein to the hotspot restores both open chromatin conformation and DSB formation. The chromatin configuration of Ty elements precludes initiation of recombination, thus preventing potentially lethal exchanges between repeated sequences.

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The compact chromatin structure of a Ty repeated sequence suppresses recombination hotspot activity in Saccharomyces cerevisiae

Abstract

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