Cohesin-mediated chromatin folding constrains homology search during DNA repair

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20m
Présentation orale

Speaker

Dr HELENE BORDELET ( Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, 75015 Paris, France / Univ Lyon, ENS, UCBL, CNRS, INSERM, Laboratory of Biology and Modelling of the Cell, UMR5239, U 1210, F-69364, Lyon, France)

Description

DNA break repair by homologous recombination (HR) entails a search for homology carried out by a specialized nucleoprotein filament (NPF). The search mechanism remains elusive, notably its interplay with the folding of chromatin in the nucleus. We show in the tractable model system S. cerevisiae that it takes place in the reorganized context of individualized metaphase-like chromosomes structured by cohesins into arrays of chromatin loops. Functionally, cohesin-mediated chromatin folding primarily constrains homology search intra-chromosomally, which provides a kinetic advantage for DNA strand invasion at intra- over inter-chromosomal donors. The sister chromatid plays a secondary inhibitory function. Using a pds5 mutant to artificially enlarge cohesin loops, we further show that the DSB region acts as a cohesin (and thus directional loop expansion) barrier, which promotes donor identification in cis. Cohesin thus constrains homology search intra-chromosomally in multiple ways, inhibiting and orienting genome-wide homology search.

Primary authors

AGNES THIERRY ( Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, 75015 Paris, France) Dr AURELE PIAZZA ( Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, 75015 Paris, France /Univ Lyon, ENS, UCBL, CNRS, INSERM, Laboratory of Biology and Modelling of the Cell, UMR5239, U 1210, F-69364, Lyon, France) GIRARD FABIEN ( Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, 75015 Paris, France) Dr HELENE BORDELET ( Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, 75015 Paris, France / Univ Lyon, ENS, UCBL, CNRS, INSERM, Laboratory of Biology and Modelling of the Cell, UMR5239, U 1210, F-69364, Lyon, France) Dr JEROME SAVOCCO (Univ Lyon, ENS, UCBL, CNRS, INSERM, Laboratory of Biology and Modelling of the Cell, UMR5239, U 1210, F-69364, Lyon, France) Dr ROMAIN KOSZUL ( Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, 75015 Paris, France)

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