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

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 enha...

Full description

Saved in:
Bibliographic Details
Published inGenes & development Vol. 33; no. 15-16; pp. 1008 - 1026
Main Authors Gómez-González, Belén, Aguilera, Andrés
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.08.2019
Subjects
DNA Replication - physiology
Genome - genetics
Genomic Instability - genetics
Humans
Neoplasms - physiopathology
Special Section: Review
Transcription Elongation, Genetic - physiology
Transcription, Genetic - physiology
genetic instability
replication fork stalling
chromosome fragility
transcription
DNA–RNA hybrids
Online AccessGet full text
ISSN0890-9369
1549-5477
1549-5477
DOI10.1101/gad.324517.119

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:0890-9369
1549-5477
1549-5477
DOI:10.1101/gad.324517.119