Cited by 159DNA Repair MechanismsMicrotubule and mitosis dynamicsCancer-related Molecular Pathways

Mechanisms of replication fork protection: a safeguard for genome stability

Errico, Alessia, Costanzo, Vincenzo·2012·Critical Reviews in Biochemistry and Molecular Biology

Abstract

During S-phase, the genome is extremely vulnerable and the progression of replication forks is often threatened by exogenous and endogenous challenges. When replication fork progression is halted, the intra S-phase checkpoint is activated to promote structural stability of stalled forks, preventing the dissociation of replisome components. This ensures the rapid resumption of replication following DNA repair. Failure in protecting and/or restarting the stalled forks contributes to alterations of the genome. Several human genetic diseases coupled to an increased cancer predisposition are caused by mutations in genes involved in safeguarding genome integrity during DNA replication. Both the ATR (ataxia telangiectasia and Rad3-related protein) kinase and the Replication pausing complex (RPC) components Tipin, Tim1 and Claspin play key roles in activating the intra S-phase checkpoint and in stabilizing the stalled replication forks. Here, we discuss the specific contribution of these factors in preserving fork structure and ensuring accurate completion of DNA replication.

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Crossref · 10.3109/10409238.2012.655374

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Authors
Errico, A., & Costanzo, V.
Affiliations
DNA damage and Genome Stability Unit, Clare Hall Laboratories, London Research Institute
Corresponding author
Costanzo, Vincenzo
Venue
Critical Reviews in Biochemistry and Molecular Biology
Published
2012-02-11
Volume
47
Issue
3
Pages
222-235
ISSN
  • 0045-6411 (ISSN-L)
  • 1040-9238
  • 1549-7798
OpenAlex
W2054468210
Cited by
159
References
170
Citations by year
2026: 4 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 12 · 2021: 15 · 2020: 9 · 2019: 10 · 2018: 12 · 2017: 19 · 2016: 15 · 2015: 14 · 2014: 20 · 2013: 16
FWCI
1.46
Type
journal article
Language
en
Open access
closed
Locations
  • Critical Reviews in Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cancer Research UK
  • Lister Institute of Preventive Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
replication fork protection, genome stability, S-phase checkpoint, replication fork restart, ATR kinase, TIPIN, TIM-1, Claspin, replisome, DNA repair, cancer predisposition syndromes, DNA replication
MeSH terms
Hepatitis A Virus Cellular Receptor 1, MRE11 Homologue Protein, Chromatids, DNA Damage, DNA Repair, DNA Replication, DNA-Binding Proteins, Humans, Membrane Glycoproteins, Phosphorylation, Receptors, Virus, Signal Transduction, Genome, Human, Protein Serine-Threonine Kinases, Replication Origin, Cell Cycle Proteins, Genetic Diseases, Inborn, Genomic Instability, Adaptor Proteins, Signal Transducing, S Phase Cell Cycle Checkpoints, Ataxia Telangiectasia Mutated Proteins

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