DNA Helicase Mph1FANCM Ensures Meiotic Recombination between Parental Chromosomes by Dissociating Precocious Displacement Loops

Meiotic pairing between parental chromosomes (homologs) is required for formation of haploid gametes. Homolog pairing depends on recombination initiation via programmed double-strand breaks (DSBs). Although DSBs appear prior to pairing, the homolog, rather than the sister chromatid, is used as repai...

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Veröffentlicht in:Developmental cell 2020-05, Vol.53 (4), p.458-472.e5
Hauptverfasser: Sandhu, Rima, Monge Neria, Francisco, Monge Neria, Jesús, Chen, Xiangyu, Hollingsworth, Nancy M., Börner, G. Valentin
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Sprache:eng
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Zusammenfassung:Meiotic pairing between parental chromosomes (homologs) is required for formation of haploid gametes. Homolog pairing depends on recombination initiation via programmed double-strand breaks (DSBs). Although DSBs appear prior to pairing, the homolog, rather than the sister chromatid, is used as repair partner for crossing over. Here, we show that Mph1, the budding yeast ortholog of Fanconi anemia helicase FANCM, prevents precocious DSB strand exchange between sister chromatids before homologs have completed pairing. By dissociating precocious DNA displacement loops (D-loops) between sister chromatids, Mph1FANCM ensures high levels of crossovers and non-crossovers between homologs. Later-occurring recombination events are protected from Mph1-mediated dissociation by synapsis protein Zip1. Increased intersister repair in absence of Mph1 triggers a shift among remaining interhomolog events from non-crossovers to crossover-specific strand exchange, explaining Mph1’s apparent anti-crossover function. Our findings identify temporal coordination between DSB strand exchange and homolog pairing as a critical determinant for recombination outcome. [Display omitted] •Meiotic double-strand breaks form D-loops following pairing of parental chromosomes•DNA helicase Mph1FANCM dissociates precocious D-loops between sister chromatids•Intersister repair due to lack of Mph1 triggers a non-crossover-to-crossover shift•Synapsis protein Zip1 protects D-loops between parental chromosomes from Mph1 During meiosis, self-inflicted double-strand breaks (DSBs) are required for pairing between parental chromosomes (homologs). Sandhu et al. now demonstrate that the yeast Fanconi anemia DNA helicase FANCM dissociates precocious DSB strand exchange between sister chromatids, thereby ensuring normal exchange between homologs.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2020.04.010