Transcription-mediated replication hindrance: a major driver of genome instability
- Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas-Universidad Pablo de Olavide., 41092 Seville, Spain
- Corresponding author: aguilo{at}us.es
Abstract
Genome replication involves dealing with obstacles that can result from DNA damage but also from chromatin alterations, topological stress, tightly bound proteins or non-B DNA structures such as R loops. Experimental evidence reveals that an engaged transcription machinery at the DNA can either enhance such obstacles or be an obstacle itself. Thus, transcription can become a potentially hazardous process promoting localized replication fork hindrance and stress, which would ultimately cause genome instability, a hallmark of cancer cells. Understanding the causes behind transcription–replication conflicts as well as how the cell resolves them to sustain genome integrity is the aim of this review.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.324517.119.
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Freely available online through the Genes & Development Open Access option.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.