Article
The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants
Author/s | Gómez González, Belén
Felipe Abrio, Irene Aguilera López, Andrés |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2009 |
Deposit Date | 2017-07-04 |
Published in |
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Abstract | Cotranscriptional 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 ... Cotranscriptional 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 replication factor C- and PCNA-like complexes. Under replicative stress, R-loop-forming THO null mutants require functional S-phase checkpoint functions but not double-strand-break repair functions for survival. Furthermore, R-loop-forming hpr1 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 the 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 |
Funding agencies | Ministerio de Ciencia e Innovación (MICIN). España Junta de Andalucía |
Project ID. | BFU2006-05260
CDS2007-0015 CVI-624 BIO-102 |
Citation | Gómez González, B., Felipe Abrio, I. y Aguilera López, A. (2009). The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Molecular and Cellular Biology, 29 (19), 5203-5213. |
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The s-phase.pdf | 2.410Mb | [PDF] | View/ | |