title: Transcription as a Threat to Genome Integrity.
abstract: Genomes undergo different types of sporadic alterations, including DNA damage, point mutations, and genome rearrangements, that constitute the basis for evolution. However, these changes may occur at high levels as a result of cell pathology and trigger genome instability, a hallmark of cancer and a number of genetic diseases. In the last two decades, evidence has accumulated that transcription constitutes an important natural source of DNA metabolic errors that can compromise the integrity of the genome. Transcription can create the conditions for high levels of mutations and recombination by its ability to open the DNA structure and remodel chromatin, making it more accessible to DNA insulting agents, and by its ability to become a barrier to DNA replication. Here we review the molecular basis of such events from a mechanistic perspective with particular emphasis on the role of transcription as a genome instability determinant.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla, Sevilla 41092, Spain; email: gaillard@us.es , aguilo@us.es.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gaillard
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla, Sevilla 41092, Spain; email: gaillard@us.es , aguilo@us.es.
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D004261:DNA Replication; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009690:Nucleic Acid Conformation; D011995:Recombination, Genetic; D014158:Transcription, Genetic
chemical_list: D004247:DNA
keywords: DNA damage; R loops; genome instability; transcription-associated mutagenesis; transcription-associated recombination; transcription–replication conflicts