The plasticity of DNA replication forks in response to clinically relevant genotoxic stress

Complete and accurate DNA replication requires the progression of replication forks through DNA damage, actively transcribed regions, structured DNA and compact chromatin. Recent studies have revealed a remarkable plasticity of the replication process in dealing with these obstacles, which includes...

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Published in:Nature reviews. Molecular cell biology Vol. 21; no. 10; pp. 633 - 651
Main Authors: Berti, Matteo, Cortez, David, Lopes, Massimo
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.10.2020
Subjects:
Adaptation
Animals
Barriers
Carcinogenesis - genetics
Chromatin
Chromatin - genetics
Crosstalk
Deoxyribonucleic acid
DNA
DNA - genetics
DNA biosynthesis
DNA damage
DNA Damage - genetics
DNA Replication - genetics
Functional morphology
Genotoxicity
Humans
Immunity
Immunity, Innate - genetics
Innate immunity
Plastic properties
Plasticity
Replication
Replication forks
Replication Origin - genetics
Replication origins
Structural damage
Tumorigenesis
ISSN:1471-0072, 1471-0080, 1471-0080
Online Access:Get full text
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Summary:Complete and accurate DNA replication requires the progression of replication forks through DNA damage, actively transcribed regions, structured DNA and compact chromatin. Recent studies have revealed a remarkable plasticity of the replication process in dealing with these obstacles, which includes modulation of replication origin firing, of the architecture of replication forks, and of the functional organization of the replication machinery in response to replication stress. However, these specialized mechanisms also expose cells to potentially dangerous transactions while replicating DNA. In this Review, we discuss how replication forks are actively stalled, remodelled, processed, protected and restarted in response to specific types of stress. We also discuss adaptations of the replication machinery and the role of chromatin modifications during these transactions. Finally, we discuss interesting recent data on the relevance of replication fork plasticity to human health, covering its role in tumorigenesis, its crosstalk with innate immunity responses and its potential as an effective cancer therapy target.
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ISSN:1471-0072
1471-0080
1471-0080
DOI:10.1038/s41580-020-0257-5