Elsevier

Experimental Cell Research

Volume 329, Issue 1, 15 November 2014, Pages 85-93
Experimental Cell Research

Review Article
DNA replication stress: Causes, resolution and disease

https://doi.org/10.1016/j.yexcr.2014.09.030Get rights and content
Under a Creative Commons license
open access

Highlights

  • Replication stress from endogenous and exogenous sources cause genomic instability.

  • ATM and ATR are major kinases involved in signaling replication stress.

  • Defects in the resolution of replication stress can cause human disease.

Abstract

DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field.

Abbreviations

pre-RC
pre-replicative complex
CFS
common fragile site
DSB
DNA double strand break
CMG complex
Cdc45.Mcm2–7.GINS
ERFS
early-replicating fragile site
DDR
DNA damage response
ssDNA
single-stranded DNA
IR
ionizing radiation
HGPS
Hutchinson–Gilford progeria syndrome
SIOD
Schimke immune-osseous dysplasia
AOA1
Apraxia Oculomotor Ataxia 1
FA
Fanconi anemia
iPOND
Isolation of protein on nascent DNA
BLESS
direct in situ breaks labeling, enrichment on streptavidin and next-generation sequencing
CRISPR
Clustered regulatory interspaced short palindromic repeats

Keywords

DNA replication
DNA damage signaling
Replication stress
Genome stability
Chromosome fragile sites

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