Anoxia Tolerant DNA Replication is Supported by ATR Kinase in the Annual Killifish Austrofundulus Limnaeus

Authors

• Riley Roth-Carter, Portland State University 1 Department of Biology P.O. Box 751 Portland OR 97207
• Erin Helms, Oregon Health and Science University 2 Division of Oncological Sciences , , 2720 S Moody Ave., Portland, OR 97201 ,
• Joshua C. Saldivar, Oregon Health and Science University 2 Division of Oncological Sciences , , 2720 S Moody Ave., Portland, OR 97201 ,
• Jason Podrabsky, Portland State University 1 Department of Biology P.O. Box 751 Portland OR 97207Follow

Published In

Journal of Cell Science

Document Type

Article

Publication Date

7-15-2026

Subjects

Anoxia, Stress tolerance, Proteomics, Anoxia tolerance, Anoxia recovery, Mitochondrial metabolism

Abstract

Hypoxia and anoxia suppress cell proliferation due to an increase in replication stress and activation of DNA damage checkpoints. Embryos of the annual killifish Austrofundulus limnaeus tolerate prolonged anoxia, indicating improved genomic stability under oxygen starvation. We investigated the cell cycle regulation of the anoxia tolerant killifish embryonic cell line PSU-AL-WS40NE during anoxia. Live-cell imaging confirms continued proliferation of WS40NE cells for the first 24 h of anoxia with minimal cell death. Fluorescence imaging shows that cells accumulate in G1 after the first day in anoxia with a rapid entry into S phase upon reoxygenation. Pharmacological inhibition shows a reliance on ataxia telangiectasia and Rad3 related (ATR) signaling, suggesting that increased γH2AX levels are driven by replication stress instead of DNA damage. This conclusion is supported by a lack of induction of a G2 checkpoint, suggesting minimal DNA damage during anoxic exposure. Maintaining cellular proliferation during anoxia and accumulating cells in the G1 phase for extended anoxic exposure is likely one way that embryos of the killifish can survive prolonged anoxia, which provides insight into mechanisms that enable cells to proliferate under metabolic stress.

Rights

Copyright (c) 2026 The Authors

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

Locate the Document

https://doi.org/10.1242/jcs.264892

DOI

10.1242/jcs.264892

Persistent Identifier

https://archives.pdx.edu/ds/psu/45186

Citation Details

Roth-Carter, R., Helms, E., Saldivar, J. C., & Podrabsky, J. (2026). Anoxia tolerant DNA replication is supported by ATR kinase in the annual killifish Austrofundulus limnaeus. Journal of Cell Science, 139(14).