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

Autor:	Cañas JC; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain., García-Rubio ML; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain., García A; Instituto de Biología Funcional y Genómica (IBFG), CSIC-Universidad de Salamanca, 37007 Salamanca, Spain., Antequera F; Instituto de Biología Funcional y Genómica (IBFG), CSIC-Universidad de Salamanca, 37007 Salamanca, Spain., Gómez-González B; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain., Aguilera A; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.
Jazyk:	angličtina
Zdroj:	Genetics [Genetics] 2022 Aug 30; Vol. 222 (1).
DOI:	10.1093/genetics/iyac108
Abstrakt:	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. (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)
Databáze:	MEDLINE
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