Novel RNA and DNA strand exchange activity of the PALB2 DNA Binding Domain and its critical role for DNA repair in cells
- Saint Louis University School of Medicine, United States
- CHU de Québec-Université Laval, Canada
- Dalhousie University, Canada
Abstract
BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumor suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
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Funding
Siteman Cancer Center
- Sergey Korolev
Foundation for Barnes-Jewish Hospital
- Sergey Korolev
Canadian Institutes of Health Research
- Jean-Yves Masson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Deveryshetty et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Novel RNA and DNA strand exchange activity of the PALB2 DNA Binding Domain and its critical role for DNA repair in cells
eLife 8:e44063.
https://doi.org/10.7554/eLife.44063
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