Monica M. Olcina
Replication stress and chromatin context link ATM activation to a role in DNA replication
Olcina, Monica M.; Foskolou, Iosifina P.; Anbalagan, Selvakumar; Senra, Joana M.; Pires, Isabel M.; Jiang, Yanyan; Ryan, Anderson J.; Hammond, Ester M.
Authors
Iosifina P. Foskolou
Selvakumar Anbalagan
Joana M. Senra
Isabel M. Pires
Yanyan Jiang
Anderson J. Ryan
Ester M. Hammond
Abstract
ATM-mediated signaling in response to DNA damage is a barrier to tumorigenesis. Here we asked whether replication stress could also contribute to ATM signaling. We demonstrate that, in the absence of DNA damage, ATM responds to replication stress in a hypoxia-induced heterochromatin-like context. In certain hypoxic conditions, replication stress occurs in the absence of detectable DNA damage. Hypoxia also induces H3K9me3, a histone modification associated with gene repression and heterochromatin. Hypoxia-induced replication stress together with increased H3K9me3 leads to ATM activation. Importantly, ATM prevents the accumulation of DNA damage in hypoxia. Most significantly, we describe a stress-specific role for ATM in maintaining DNA replication rates in a background of increased H3K9me3. Furthermore, the ATM-mediated response to oncogene-induced replication stress is enhanced in hypoxic conditions. Together, these data indicate that hypoxia plays a critical role in the activation of the DNA damage response, therefore contributing to this barrier to tumorigenesis.
Citation
Olcina, M. M., Foskolou, I. P., Anbalagan, S., Senra, J. M., Pires, I. M., Jiang, Y., Ryan, A. J., & Hammond, E. M. (2013). Replication stress and chromatin context link ATM activation to a role in DNA replication. Molecular cell, 52(5), 758-766. https://doi.org/10.1016/j.molcel.2013.10.019
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 17, 2013 |
Online Publication Date | Nov 21, 2013 |
Publication Date | Nov 21, 2013 |
Deposit Date | Mar 21, 2018 |
Publicly Available Date | Apr 3, 2018 |
Journal | Molecular Cell |
Print ISSN | 1097-2765 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 52 |
Issue | 5 |
Pages | 758-766 |
DOI | https://doi.org/10.1016/j.molcel.2013.10.019 |
Keywords | Cell Biology; Molecular Biology |
Public URL | https://hull-repository.worktribe.com/output/749227 |
Publisher URL | http://www.cell.com/molecular-cell/abstract/S1097-2765(13)00785-5 |
Additional Information | This article is maintained by: Elsevier; Article Title: Replication Stress and Chromatin Context Link ATM Activation to a Role in DNA Replication; Journal Title: Molecular Cell; CrossRef DOI link to publisher maintained version: http://dx.doi.org/10.1016/j.molcel.2013.10.019; Content Type: article; Copyright: Copyright © 2013 The Authors. Published by Elsevier Inc. |
Contract Date | Apr 3, 2018 |
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
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