A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability

The stability of the genome is occasionally challenged by the formation of DNA-RNA hybrids and R-loops, which can be influenced by the chromatin context. This is mainly due to the fact that DNA-RNA hybrids hamper the progression of replication forks, leading to fork stalling and, ultimately, DNA bre...

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Detalles Bibliográficos
Autores: Cañas, Juan Carlos, García Rubio, María Luisa, García, Alicia, Antequera, Francisco, Gómez González, Belén, Aguilera López, Andrés
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/137151
Acceso en línea:https://hdl.handle.net/11441/137151
https://doi.org/10.1093/genetics/iyac108
Access Level:acceso abierto
Palabra clave:DNA–RNA hybrids
Genetic instability
Histone acetylation
R-loops
Sister-chromatid recombination
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spelling A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instabilityCañas, Juan CarlosGarcía Rubio, María LuisaGarcía, AliciaAntequera, FranciscoGómez González, BelénAguilera López, AndrésDNA–RNA hybridsGenetic instabilityHistone acetylationR-loopsSister-chromatid recombinationThe stability of the genome is occasionally challenged by the formation of DNA-RNA hybrids and R-loops, which can be influenced by the chromatin context. This is mainly due to the fact that DNA-RNA hybrids hamper the progression of replication forks, leading to fork stalling and, ultimately, DNA breaks. Through a specific screening of chromatin modifiers performed in the yeast Saccharomyces cerevisiae, we have found that the Rtt109 histone acetyltransferase is involved in several steps of R-loop-metabolism and their associated genetic instability. On the one hand, Rtt109 prevents DNA-RNA hybridization by the acetylation of histone H3 lysines 14 and 23 and, on the other hand, it is involved in the repair of replication-born DNA breaks, such as those that can be caused by R-loops, by acetylating lysines 14 and 56. In addition, Rtt109 loss renders cells highly sensitive to replication stress in combination with R-loop-accumulating THO-complex mutants. Our data evidence that the chromatin context simultaneously influences the occurrence of DNA-RNA hybrid-associated DNA damage and its repair, adding complexity to the source of R-loop-associated genetic instability.European Research Council ERC2014 AdG669898 TARLOOPMinisterio de Economía y Competitividad BFU2016-75058-PMinisterio de Ciencia e Innovación PID2019-104270GB-I00, PID2020-118423GB-I00European Union US-1258654Junta de Andalucía P12-BIO-1238Genetics Society of AmericaGenéticaEuropean Research Council (ERC)Ministerio de Economía y Competitividad (MINECO). EspañaMinisterio de Ciencia e Innovación (MICIN). EspañaEuropean Union (UE)Junta de Andalucía2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/137151https://doi.org/10.1093/genetics/iyac108reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésGenetics, 222 (1), iyac108.ERC2014 AdG669898 TARLOOPBFU2016-75058-PPID2019-104270GB-I00PID2020-118423GB-I00US-1258654P12-BIO-1238https://doi.org/10.1093/genetics/iyac108info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1371512026-06-17T12:51:07Z
dc.title.none.fl_str_mv A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
title A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
spellingShingle A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
Cañas, Juan Carlos
DNA–RNA hybrids
Genetic instability
Histone acetylation
R-loops
Sister-chromatid recombination
title_short A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
title_full A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
title_fullStr A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
title_full_unstemmed A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
title_sort A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
dc.creator.none.fl_str_mv Cañas, Juan Carlos
García Rubio, María Luisa
García, Alicia
Antequera, Francisco
Gómez González, Belén
Aguilera López, Andrés
author Cañas, Juan Carlos
author_facet Cañas, Juan Carlos
García Rubio, María Luisa
García, Alicia
Antequera, Francisco
Gómez González, Belén
Aguilera López, Andrés
author_role author
author2 García Rubio, María Luisa
García, Alicia
Antequera, Francisco
Gómez González, Belén
Aguilera López, Andrés
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Genética
European Research Council (ERC)
Ministerio de Economía y Competitividad (MINECO). España
Ministerio de Ciencia e Innovación (MICIN). España
European Union (UE)
Junta de Andalucía
dc.subject.none.fl_str_mv DNA–RNA hybrids
Genetic instability
Histone acetylation
R-loops
Sister-chromatid recombination
topic DNA–RNA hybrids
Genetic instability
Histone acetylation
R-loops
Sister-chromatid recombination
description The stability of the genome is occasionally challenged by the formation of DNA-RNA hybrids and R-loops, which can be influenced by the chromatin context. This is mainly due to the fact that DNA-RNA hybrids hamper the progression of replication forks, leading to fork stalling and, ultimately, DNA breaks. Through a specific screening of chromatin modifiers performed in the yeast Saccharomyces cerevisiae, we have found that the Rtt109 histone acetyltransferase is involved in several steps of R-loop-metabolism and their associated genetic instability. On the one hand, Rtt109 prevents DNA-RNA hybridization by the acetylation of histone H3 lysines 14 and 23 and, on the other hand, it is involved in the repair of replication-born DNA breaks, such as those that can be caused by R-loops, by acetylating lysines 14 and 56. In addition, Rtt109 loss renders cells highly sensitive to replication stress in combination with R-loop-accumulating THO-complex mutants. Our data evidence that the chromatin context simultaneously influences the occurrence of DNA-RNA hybrid-associated DNA damage and its repair, adding complexity to the source of R-loop-associated genetic instability.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/137151
https://doi.org/10.1093/genetics/iyac108
url https://hdl.handle.net/11441/137151
https://doi.org/10.1093/genetics/iyac108
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genetics, 222 (1), iyac108.
ERC2014 AdG669898 TARLOOP
BFU2016-75058-P
PID2019-104270GB-I00
PID2020-118423GB-I00
US-1258654
P12-BIO-1238
https://doi.org/10.1093/genetics/iyac108
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Genetics Society of America
publisher.none.fl_str_mv Genetics Society of America
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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