UMMS Affiliation

Department of Surgery

Publication Date

2019-04-16

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Cells | Enzymes and Coenzymes | Fungi | Genetic Phenomena | Molecular Biology | Structural Biology

Abstract

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.

Keywords

Acetylation, Chromatin, DNA replication, Histone H4, Mst1, NuA4, Replication fork protection complex, Replication forks, Schizosaccharomyces pombe, Swi1, Timeless, Vid21

Rights and Permissions

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

10.1186/s13072-019-0271-z

Source

Epigenetics Chromatin. 2019 Apr 16;12(1):24. doi: 10.1186/s13072-019-0271-z. Link to article on publisher's site

Journal/Book/Conference Title

Epigenetics and chromatin

Related Resources

Link to Article in PubMed

PubMed ID

30992049

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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