Dear Colleagues,

The essential process of gene expression poses a threat to the integrity of the genome. As was first observed in the early 1980s both in prokaryotes and eukaryotes, the stability of a particular DNA sequence is challenged during its transcription. Since then, a growing body of research has nurtured our knowledge of the causes behind this phenomenon of transcription-associated genetic instability, including a major accessibility of the transcribed chromatin to genotoxins or DNA-modifying enzymes. Moreover, the process of transcription inherently affects the topology of the DNA, exerts changes in the chromatin landscape, and favors the formation of certain DNA-secondary structures, such as DNA–RNA hybrids, all of which can trigger transcription–replication conflicts. Although the replication machinery has evolved to deal with transcribed chromatin, it can stall upon this encounter, frequently requiring fork protection and re-start mechanisms.

There are specific repair mechanisms that deal with lesions occurring during transcription, and the occurrence of transcription is often spatial and temporally regulated to minimize its interference with other metabolic processes such as replication. However, a number of factors function to solve and prevent the harmful effects of transcription, underscoring the relevance of this menace for genome stability. The consequences of this vulnerability include higher levels of mutation, recombination, DNA breaks, chromosomal translocations, and other rearrangements, all of which have been related to the fragility of certain transcribed regions of the DNA and which can account for cell death or massive genomic interchanges possibly illuminating the origin of human diseases, such as neurodegeneration or cancer.

This Special Issue of Life aims to compile the current research and views of different laboratories regarding the state-of-the-art of the phenomenon of ‘Transcription-associated Genetic Instability’, summarizing the understanding of its main causes and consequences and the factors and pathways that altogether contribute to make DNA a stable information unit compatible with gene expression.

Dr. Belén Gómez González
Guest Editor

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• Transcription-associated recombination
• Transcription-associated mutation
• Transcription-induced chromosomal translocations
• DNA–RNA hybrids
• R-loops
• Fragile sites
• Spatiotemporal regulation of transcription and replication
• Transcription–replication conflicts
• Replication fork protection and re-start mechanisms
• Transcription-associated genetic instability and disease