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Rodriguez-Pastrana, I., Birli, E. and Coutts, A.S. 
ORCID: 0000-0002-5005-1864,
2023.
p53-dependent DNA repair during the DNA damage response requires actin nucleation by JMY.
Cell Death and Differentiation, 30 (7), pp. 1636-1647.
ISSN 1350-9047
Abstract
The tumour suppressor p53 is a nuclear transcription factor with key roles during DNA damage to enable a variety of cellular responses including cell cycle arrest, apoptosis and DNA repair. JMY is an actin nucleator and DNA damage-responsive protein whose sub-cellular localisation is responsive to stress and during DNA damage JMY undergoes nuclear accumulation. To gain an understanding of the wider role for nuclear JMY in transcriptional regulation, we performed transcriptomics to identify JMY-mediated changes in gene expression during the DNA damage response. We show that JMY is required for effective regulation of key p53 target genes involved in DNA repair, including XPC, XRCC5 (Ku80) and TP53I3 (PIG3). Moreover, JMY depletion or knockout leads to increased DNA damage and nuclear JMY requires its Arp2/3-dependent actin nucleation function to promote the clearance of DNA lesions. In human patient samples a lack of JMY is associated with increased tumour mutation count and in cells results in reduced cell survival and increased sensitivity to DNA damage response kinase inhibition. Collectively, we demonstrate that JMY enables p53-dependent DNA repair under genotoxic stress and suggest a role for actin in JMY nuclear activity during the DNA damage response.
| Item Type: | Journal article | ||||||
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| Publication Title: | Cell Death and Differentiation | ||||||
| Creators: | Rodriguez-Pastrana, I., Birli, E. and Coutts, A.S. | ||||||
| Publisher: | Springer Nature | ||||||
| Date: | July 2023 | ||||||
| Volume: | 30 | ||||||
| Number: | 7 | ||||||
| ISSN: | 1350-9047 | ||||||
| Identifiers: |
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| Rights: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Jonathan Gallacher | ||||||
| Date Added: | 20 Nov 2023 09:47 | ||||||
| Last Modified: | 20 Nov 2023 09:47 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/50396 |
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