Journal
MOLECULAR CELL
Volume 73, Issue 6, Pages 1255-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2019.01.005
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Funding
- ARC Foundation
- EMBO [ALTF-238-2013]
- European Union [628355]
- Philippe Foundation
- NIH [GM58015, CA92276]
- Agence Nationale pour la Recherche grant [ANR-13-BSV6-0012-02]
- [P30 CA93373]
- Agence Nationale de la Recherche (ANR) [ANR-13-BSV6-0012] Funding Source: Agence Nationale de la Recherche (ANR)
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Displacement loops (D-loops) are pivotal intermediates of homologous recombination (HR), a universal DNA double strand break (DSB) repair pathway. We developed a versatile assay for the physical detection of D-loops in vivo, which enabled studying the kinetics of their formation and defining the activities controlling their metabolism. Nascent D-loops are detected within 2 h of DSB formation and extended in a delayed fashion in a genetic system designed to preclude downstream repair steps. The majority of nascent D-loops are disrupted by two pathways: one supported by the Srs2 helicase and the other by the Mph1 helicase and the Sgs1-Top3-Rmi1 helicase-topoisomerase complex. Both pathways operate without significant overlap and are delineated by the Rad54 paralog Rdh54 in an ATPase-independent fashion. This study uncovers a layer of quality control of HR relying on nascent D-loop dynamics.
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