Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis.

Molecular cell 2019 Aug 22

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Homologous recombination (HR) is essential for high-fidelity DNA repair during mitotic proliferation and meiosis. Yet, context-specific modifications must tailor the recombination machinery to avoid (mitosis) or enforce (meiosis) the formation of reciprocal exchanges-crossovers-between recombining chromosomes. To obtain molecular insight into how crossover control is achieved, we affinity purified 7 DNA-processing enzymes that channel HR intermediates into crossovers or noncrossovers from vegetative cells or cells undergoing meiosis. Using mass spectrometry, we provide a global characterization of their composition and reveal mitosis- and meiosis-specific modules in the interaction networks. Functional analyses of meiosis-specific interactors of MutLγ-Exo1 identified Rtk1, Caf120, and Chd1 as regulators of crossing-over. Chd1, which transiently associates with Exo1 at the prophase-to-metaphase I transition, enables the formation of MutLγ-dependent crossovers through its conserved ability to bind and displace nucleosomes. Thus, rewiring of the HR network, coupled to chromatin remodeling, promotes context-specific control of the recombination outcome. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Philipp Wild, Aitor Susperregui, Ilaria Piazza, Christian Dörig, Ashwini Oke, Meret Arter, Miyuki Yamaguchi, Alexander T Hilditch, Karla Vuina, Ki Choi Chan, Tatiana Gromova, James E Haber, Jennifer C Fung, Paola Picotti, Joao Matos. Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis. Molecular cell. 2019 Aug 22;75(4):859-874.e4