Department of Surgery
Amino Acids, Peptides, and Proteins | Biochemistry | Cells | Enzymes and Coenzymes | Fungi | Genetic Phenomena | Molecular Biology | Structural Biology
BACKGROUND: Histone acetylation plays an important role in DNA replication and repair because replicating chromatin is subject to dynamic changes in its structures. However, its precise mechanism remains elusive. In this report, we describe roles of the NuA4 acetyltransferase and histone H4 acetylation in replication fork protection in the fission yeast Schizosaccharomyces pombe.
RESULTS: Downregulation of NuA4 subunits renders cells highly sensitive to camptothecin, a compound that induces replication fork breakage. Defects in NuA4 function or mutations in histone H4 acetylation sites lead to impaired recovery of collapsed replication forks and elevated levels of Rad52 DNA repair foci, indicating the role of histone H4 acetylation in DNA replication and fork repair. We also show that Vid21 interacts with the Swi1-Swi3 replication fork protection complex and that Swi1 stabilizes Vid21 and promotes efficient histone H4 acetylation. Furthermore, our genetic analysis demonstrates that loss of Swi1 further sensitizes NuA4 and histone H4 mutant cells to replication fork breakage.
CONCLUSION: Considering that Swi1 plays a critical role in replication fork protection, our results indicate that NuA4 and histone H4 acetylation promote repair of broken DNA replication forks.
Acetylation, Chromatin, DNA replication, Histone H4, Mst1, NuA4, Replication fork protection complex, Replication forks, Schizosaccharomyces pombe, Swi1, Timeless, Vid21
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Copyright © The Author(s) 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
Epigenetics Chromatin. 2019 Apr 16;12(1):24. doi: 10.1186/s13072-019-0271-z. Link to article on publisher's site
Epigenetics and chromatin
Noguchi C, Singh T, Ziegler MA, Peake JD, Khair L, Aza A, Nakamura TM, Noguchi E. (2019). The NuA4 acetyltransferase and histone H4 acetylation promote replication recovery after topoisomerase I-poisoning. Open Access Publications by UMass Chan Authors. https://doi.org/10.1186/s13072-019-0271-z. Retrieved from https://escholarship.umassmed.edu/oapubs/3825
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This work is licensed under a Creative Commons Attribution 4.0 License.
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