Journal
MOLECULAR CELL
Volume 47, Issue 5, Pages 722-733Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2012.06.023
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Funding
- JSPS
- MEXT, Japan
- Grants-in-Aid for Scientific Research [23221005, 23657081, 21241046, 23770003, 10J08626] Funding Source: KAKEN
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Higher-order chromosome structure is assumed to control various DNA-templated reactions in eukaryotes. Meiotic chromosomes implement developed structures called axes and loops; both are suggested to tether each other, activating Spoil to catalyze meiotic DNA double-strand breaks (DSBs) at recombination hotspots. We found that the Schizosaccharomyces pombe Spo11 homolog Red 12 and its partners form two distinct subcomplexes, DSBC (Rec6-Rec12-Rec14) and SFT (Rec7-Rec15-Rec24). Mde2, whose expression is strictly regulated by the replication checkpoint, interacts with Rec15 to stabilize the SFT subcomplex and further binds Rec14 in DSBC. Rec10 provides a docking platform for SFT binding to axes and can partially interact with DSB sites located in loops depending upon Mde2, which is indicative of the formation of multiprotein-based tethered axis-loop complex. These data lead us to propose a mechanism by which Mde2 functions as a recombination initiation mediator to tether axes and loops, in liaison with the meiotic replication checkpoint.
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