RT Journal Article
T1 Histone Mutants Separate R Loop Formation from Genome Instability Induction.
A1 García-Pichardo, Desiré
A1 Cañas, Juan C
A1 García-Rubio, María L
A1 Gómez-González, Belén
A1 Rondón, Ana G
A1 Aguilera, Andrés
K1 H3 serine-10 phosphorylation
K1 R loops
K1 RNA-DNA hybrids
K1 chromatin
K1 chromatin compaction
K1 chromosome fragility
K1 genome instability
K1 histones H3 and H4
AB R loops have positive physiological roles, but they can also be deleterious by causing genome instability, and the mechanisms for this are unknown. Here we identified yeast histone H3 and H4 mutations that facilitate R loops but do not cause instability. R loops containing single-stranded DNA (ssDNA), versus RNA-DNA hybrids alone, were demonstrated using ssDNA-specific human AID and bisulfite. Notably, they are similar size regardless of whether or not they induce genome instability. Contrary to mutants causing R loop-mediated instability, these histone mutants do not accumulate H3 serine-10 phosphate (H3S10-P). We propose a two-step mechanism in which, first, an altered chromatin facilitates R loops, and second, chromatin is modified, including H3S10-P, as a requisite for compromising genome integrity. Consistently, these histone mutations suppress the high H3S10 phosphorylation and genomic instability of hpr1 and sen1 mutants. Therefore, contrary to what was previously believed, R loops do not cause genome instability by themselves.
YR 2017
FD 2017
LK http://hdl.handle.net/10668/11265
UL http://hdl.handle.net/10668/11265
LA en
DS RISalud
RD Apr 7, 2025