title: Dealing with transcriptional outbursts during S phase to protect genomic integrity.
abstract: Transcription during S phase needs to be spatially and temporally regulated to prevent collisions between the transcription and replication machineries. Cells have evolved a number of mechanisms to make both processes compatible under normal growth conditions. When conflict management fails, the head-on encounter between RNA and DNA polymerases results in genomic instability unless conflict resolution mechanisms are activated. Nevertheless, there are specific situations in which cells need to dramatically change their transcriptional landscape to adapt to environmental challenges. Signal transduction pathways, such as stress-activated protein kinases (SAPKs), serve to regulate gene expression in response to environmental insults. Prototypical members of SAPKs are the yeast Hog1 and mammalian p38. In response to stress, p38/Hog1 SAPKs control transcription and also regulate cell cycle progression. When yeast cells are stressed during S phase, Hog1 promotes gene induction and, remarkably, also delays replication by directly affecting early origin firing and fork progression. Therefore, by delaying replication, Hog1 plays a key role in preventing conflicts between RNA and DNA polymerases. In this review, we focus on the genomic determinants and mechanisms that make compatible transcription with replication during S phase to prevent genomic instability, especially in response to environmental changes.
authors.affiliation: Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, E-08003 Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Duch
authors.forename: Eulàlia
authors.initials: E
authors.lastname: de Nadal
authors.forename: Francesc
authors.initials: F
authors.lastname: Posas
mesh_terms: D004261:DNA Replication; D042822:Genomic Instability; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: RC; RFB; SAPK; TAR; cell cycle regulation; rDNA; rRNA; replication; replication complex; replication fork barrier; ribosomal DNA; ribosomal RNA; stress responses; stress-activated protein kinase; transcription; transcription-associated recombination