α-Catenin is an F-actin-binding protein widely recognized for its role in cell–cell adhesion. However, a growing body of literature indicates that α-catenin is also a nuclear protein. In this study, we show that α-catenin is able to modulate the sensitivity of cells to DNA damage and toxicity. Furthermore, nuclear α-catenin is actively recruited to sites of DNA damage. This recruitment occurs in a β-catenin-dependent manner and requires nuclear actin polymerization. These findings provide mechanistic insight into the WNT-mediated regulation of the DNA damage response and suggest a novel role for the α-catenin–β-catenin complex in the nucleus.
The authors declare no competing or financial interests.
Conceptualization: L.A.S., C.J.G., P.d.L.; Methodology: L.A.S., A.Y., C.J.G., P.d.L.; Formal analysis: L.A.S.; Investigation: L.A.S.; Resources: A.Y., C.J.G., P.d.L.; Writing - original draft: L.A.S.; Writing - review & editing: L.A.S., C.J.G., P.d.L.; Visualization: L.A.S.; Supervision: L.A.S., C.J.G., P.d.L.; Project administration: L.A.S., C.J.G., P.d.L.; Funding acquisition: L.A.S., C.J.G., P.d.L.
This work was supported by National Institutes of Health (GM80587 to P.d.L.; GM076561 to C.J.G.), the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust (to P.d.L. as co-principal investigator), the Northwestern University Physical Sciences Oncology Center associated with National Cancer Institute (U54CA143869 to C.J.G. and P.d.L.), the American Heart Association (AHA) (13PRE17050060), a Chicago Biomedical Consortium Scholar award, UIC Dean's Scholar, and Chancellor's graduate research fellowship (to L.S.). Deposited in PMC for release after 12 months.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.199893.supplemental
- Received November 18, 2016.
- Accepted March 20, 2017.
- © 2017. Published by The Company of Biologists Ltd