Proteomics

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Network rewiring of homologous recombination during mitotic proliferation and meiosis


ABSTRACT: Homologous recombination is essential for high-fidelity DNA repair during mitotic proliferation and meiosis. Yet, context-specific modifications must tailor the recombination machinery to avoid, or enforce, formation of reciprocal exchanges – crossovers – between recombining chromosomes. To obtain molecular insight into how crossover control is achieved, we affinity-purified the 7 DNA-processing enzymes with known roles in channelling HR intermediates into crossovers, or non-crossovers, from vegetative cells, or cells undergoing meiosis. Using mass spectrometry, we provide the first global characterization of their composition. The resulting mitosis- and meiosis-specific interaction maps reveal intricate changes in enzyme architecture and a concerted rewiring of the interaction networks to support flexible control to the recombination outcome. Moreover, functional analyses of 31 novel interactions uncovered 8 meiosis-specific network components that remodel HR to support crossing-over. Chd1, which transiently associates with Exo1 during meiosis, enables the formation of MutLγ-Exo1-dependent crossovers through its conserved ability to bind and displace nucleosomes.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Ilaria Piazza  

LAB HEAD: Paola Picotti

PROVIDER: PXD012486 | Pride | 2019-07-31

REPOSITORIES: Pride

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Publications


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 vegeta  ...[more]

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