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Genes Dev. 2019 May 23. doi: 10.1101/gad.324517.119. [Epub ahead of print]

Transcription-mediated replication hindrance: a major driver of genome instability.

Author information

1
Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas-Universidad Pablo de Olavide., 41092 Seville, Spain.

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.

KEYWORDS:

DNA–RNA hybrids; chromosome fragility; genetic instability; replication fork stalling; transcription

PMID:
31123061
DOI:
10.1101/gad.324517.119
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