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Transcription as a threat to genome integrity

AuthorsGaillard, Hélène ; Aguilera, Andrés
KeywordsTranscription-associated recombination
Transcription-associated mutagenesis
Transcription–replication conflicts
R loops
Genome instability
DNA damage
Issue Date2016
PublisherAnnual Reviews
CitationAnnual Review of Biochemistry 85: 291-317 (2016)
AbstractGenomes 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.
Identifiersdoi: 10.1146/annurev-biochem-060815-014908
issn: 0066-4154
e-issn: 1545-4509
Appears in Collections:(CABIMER) Artículos
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