Transcription as a Threat to Genome Integrity

Annu Rev Biochem. 2016 Jun 2;85:291-317. doi: 10.1146/annurev-biochem-060815-014908. Epub 2016 Mar 24.

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.

Keywords: DNA damage; R loops; genome instability; transcription-associated mutagenesis; transcription-associated recombination; transcription–replication conflicts.

Publication types

  • Review

MeSH terms

  • Chromatin Assembly and Disassembly
  • DNA / genetics
  • DNA / metabolism
  • DNA Breaks, Single-Stranded
  • DNA Repair*
  • DNA Replication
  • Genome, Human
  • Genomic Instability*
  • Humans
  • Mutagenesis*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Nucleic Acid Conformation
  • Recombination, Genetic
  • Transcription, Genetic*

Substances

  • DNA