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Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis

Wild, Philipp, Susperregui, Aitor, Piazza, Ilaria, Dörig, Christian, Oke, Ashwini, Arter, Meret, Yamaguchi, Miyuki, Hilditch, Alexander T., Vuina, Karla, Chan, Ki Choi, Gromova, Tatiana, Haber, James E., Fung, Jennifer C., Picotti, Paola, Matos, Joao
Molecular cell 2019 v.75 no.4 pp. 859-874.e4
DNA repair, crossing over, enzymes, homologous recombination, mass spectrometry, meiosis, mitosis, nucleosomes, vegetative cells
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.