Reference: Gomez-Gonzalez B, et al. (2009) The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Mol Cell Biol 29(19):5203-13

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Abstract

Co-transcriptional R-loops are formed in yeast mutants of the THO complex, which functions at the interface between transcription and mRNA export. Despite the relevance of R-loops in transcription-associated recombination, the mechanisms by which they trigger recombination are still elusive. In order to understand how R-loops compromise genome stability we have analyzed the genetic interaction of THO with 26 genes involved in replication, S-phase checkpoint, DNA repair and chromatin remodeling. We found a synthetic growth defect in double null mutants of THO and S-phase checkpoint factors, such as the RFC- and PCNA-like complexes. Under replicative stress, R-loop forming THO null mutants require functional S-phase checkpoint functions but not double-strand break (DSB) repair functions for survival. Furthermore, R-loop forming hpr1Delta mutants display replication fork-progression impairment at actively transcribed chromosomal regions and trigger Rad53 phosphorylation. We conclude that R-loop-mediated DNA damage activates the S-phase checkpoint, which is required for cell survival of THO mutants under replicative stress. In light of these results, we propose a model in which R-loop-mediated recombination is explained by template switching.

Reference Type
Journal Article
Authors
Gomez-Gonzalez B, Felipe-Abrio I, Aguilera A
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