Article
A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability
Author/s | Cañas, Juan Carlos
García Rubio, María Luisa ![]() ![]() ![]() ![]() ![]() ![]() ![]() García, Alicia Antequera, Francisco Gómez González, Belén ![]() ![]() ![]() ![]() ![]() ![]() ![]() Aguilera López, Andrés ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2022 |
Deposit Date | 2022-09-16 |
Published in |
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Abstract | 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 ... 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. |
Funding agencies | European Research Council (ERC) Ministerio de Economía y Competitividad (MINECO). España Ministerio de Ciencia e Innovación (MICIN). España European Union (UE) Junta de Andalucía |
Project ID. | ERC2014 AdG669898 TARLOOP
![]() BFU2016-75058-P ![]() PID2019-104270GB-I00 ![]() PID2020-118423GB-I00 ![]() US-1258654 ![]() P12-BIO-1238 ![]() |
Citation | Cañas, J.C., García Rubio, M.L., García, A., Antequera, F., Gómez González, B. y Aguilera López, A. (2022). A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability. Genetics, 222 (1), iyac108. |
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