Xing, M., Wang, X., Palmai-Pallag, T. et al. (4 more authors) (2015) Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. Oncotarget, 6 (35). pp. 37638-37646.
Abstract
The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | DNA replication; Holliday junctions; NBS1; cellular senescence; homologous recombination; Animals; Apoptosis; Cell Proliferation; Cells, Cultured; Cellular Senescence; DNA Damage; DNA Repair; DNA Replication; DNA-Binding Proteins; Endonucleases; Fibroblasts; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Mice; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; S Phase |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Apr 2020 08:15 |
Last Modified: | 09 Apr 2020 07:14 |
Status: | Published |
Publisher: | Impact Journals |
Refereed: | Yes |
Identification Number: | 10.18632/oncotarget.5497 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:159262 |