Eukaryotic cells continuously experience DNA damage that can perturb key molecular processes like DNA replication. DNA replication forks that encounter DNA lesions typically slow and may stall, which can lead to highly detrimental fork collapse if appropriate protective measures are not executed. Stabilization and protection of stalled replication forks ensures the possibility of effective fork restart and prevents genomic instability. Recent efforts from multiple laboratories have highlighted several proteins involved in replication fork remodeling and DNA damage response pathways as key regulators of fork stability. Homologous recombination factors such as RAD51, BRCA1, and BRCA2, along with components of the Fanconi Anemia pathway, are now known to be crucial for stabilizing stalled replication forks and preventing nascent strand degradation. Several checkpoint proteins have additionally been implicated in fork protection. Ongoing work in this area continues to shed light on a sophisticated molecular pathway that balances the action of DNA resection and fork protection to maintain genomic integrity, with important implications for the fate of both normal and malignant cells following replication stress.
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December 2018
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Dysfunctional cytoskeleton and neurodegeneration: novel pathways in Parkinson's disease? This image represents the degeneration of the neuronal tree during the aging process. In this issue Civiero et al. discuss the consequence of impaired cytoskeletal dynamics on neurite morphology and neuronal physiology in Parkinson's disease. For further details see pages 1653–1663.
Review Article|
December 04 2018
A tough row to hoe: when replication forks encounter DNA damage
Darshil R. Patel;
Darshil R. Patel
1Department of Biomedical Sciences, Cornell University, T2-006C Veterinary Research Tower, Ithaca, NY 14853, U.S.A.
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Robert S. Weiss
1Department of Biomedical Sciences, Cornell University, T2-006C Veterinary Research Tower, Ithaca, NY 14853, U.S.A.
Correspondence: Robert S. Weiss (rsw26@cornell.edu)
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Publisher: Portland Press Ltd
Received:
September 12 2018
Revision Received:
November 05 2018
Accepted:
November 07 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (6): 1643–1651.
Article history
Received:
September 12 2018
Revision Received:
November 05 2018
Accepted:
November 07 2018
Citation
Darshil R. Patel, Robert S. Weiss; A tough row to hoe: when replication forks encounter DNA damage. Biochem Soc Trans 17 December 2018; 46 (6): 1643–1651. doi: https://doi.org/10.1042/BST20180308
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