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bioRxiv · 10.1101/495192

Novel strand exchange activity of the human PALB2 DNA Binding Domain and its critical role for DNA repair in cells

Korolev, S.·Ryzhikov, M.·Brahati, N.·Peterlini, T.·Dellaire, G.·Masson, J.-Y.·Deveryshetty, J.
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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. They stimulate RAD51 recombinase during homology-directed repair (HDR). Along with being a hub for a protein interaction network, PALB2 interacts with DNA. The mechanism of PALB2 DNA binding and its function are poorly understood. We identified a major DNA-binding site in PALB2, mutation of which reduces the RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the RAD51 strand exchange reaction. Surprisingly, it promotes the strand exchange without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use both 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.

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Korolev, S., Ryzhikov, M., Brahati, N., Peterlini, T., Dellaire, G., Masson, J.-Y., Deveryshetty, J.. 2018-12-13. Novel strand exchange activity of the human PALB2 DNA Binding Domain and its critical role for DNA repair in cells. https://doi.org/10.1101/495192

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