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Int. J. Mol. Sci. 2018, 19(10), 2909; https://doi.org/10.3390/ijms19102909

Ubiquitylation at the Fork: Making and Breaking Chains to Complete DNA Replication

Department of Biology, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
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Received: 31 August 2018 / Revised: 20 September 2018 / Accepted: 24 September 2018 / Published: 25 September 2018
(This article belongs to the Special Issue DNA Replication Stress)
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PDF [1595 KB, uploaded 25 September 2018]
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Abstract

The complete and accurate replication of the genome is a crucial aspect of cell proliferation that is often perturbed during oncogenesis. Replication stress arising from a variety of obstacles to replication fork progression and processivity is an important contributor to genome destabilization. Accordingly, cells mount a complex response to this stress that allows the stabilization and restart of stalled replication forks and enables the full duplication of the genetic material. This response articulates itself on three important platforms, Replication Protein A/RPA-coated single-stranded DNA, the DNA polymerase processivity clamp PCNA and the FANCD2/I Fanconi Anemia complex. On these platforms, the recruitment, activation and release of a variety of genome maintenance factors is regulated by post-translational modifications including mono- and poly-ubiquitylation. Here, we review recent insights into the control of replication fork stability and restart by the ubiquitin system during replication stress with a particular focus on human cells. We highlight the roles of E3 ubiquitin ligases, ubiquitin readers and deubiquitylases that provide the required flexibility at stalled forks to select the optimal restart pathways and rescue genome stability during stressful conditions. View Full-Text
Keywords: DNA replication stress; genome stability; ubiquitin; replication fork restart; translesion synthesis; template-switching; homologous recombination; Fanconi Anemia DNA replication stress; genome stability; ubiquitin; replication fork restart; translesion synthesis; template-switching; homologous recombination; Fanconi Anemia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Yates, M.; Maréchal, A. Ubiquitylation at the Fork: Making and Breaking Chains to Complete DNA Replication. Int. J. Mol. Sci. 2018, 19, 2909.

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