RT Journal Article
T1 A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability.
A1 Cañas, Juan Carlos
A1 García-Rubio, María Luisa
A1 García, Alicia
A1 Antequera, Francisco
A1 Gómez-González, Belén
A1 Aguilera, Andrés
K1 DNA–RNA hybrids
K1 R-loops
K1 genetic instability
K1 histone acetylation
K1 sister-chromatid recombination
AB 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.
YR 2022
FD 2022
LK http://hdl.handle.net/10668/19782
UL http://hdl.handle.net/10668/19782
LA en
DS RISalud
RD Apr 11, 2025