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A Prion that regulates genome diversification

Byers, J. S.; Futia, R. A.; Elgort, A. V.; Lozanoski, T. M.; Garcia, D. M.; Jarosz, D. F.

2021-10-24 molecular biology
10.1101/2021.10.23.465590 bioRxiv
Show abstract

Epigenetic mechanisms mediate diverse gene expression programs in growth and development. Here we report a protein-based epigenetic element, a prion, formed by the conserved DNA helicase Mph1/FANCM. [MIX+] is a cytoplasmically inherited state with propagation driven by the non-amyloid prion templating of Mph1. [MIX+] provides resistance to DNA damage, a gain-of-function trait that requires helicase activity. [MIX+] reduces mitotic mutation rates, but promotes meiotic crossovers, driving measurable phenotypic diversification in wild outcrosses. Remarkably, [MIX+] can be induced by DNA-damaging stresses in which it is beneficial. Thus, [MIX+] fuels a quasi-Lamarckian form of inheritance that promotes survival of the current generation and diversification of the next.

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