A central coupler for recombination initiation linking chromosome architecture to s phase checkpoint |
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Authors: | Tomoichiro Miyoshi Masaru Ito Kazuto Kugou Shintaro Yamada Masaki Furuichi Arisa Oda Takatomi Yamada Kouji Hirota Hisao Masai Kunihiro Ohta |
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Institution: | Department of Life Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan. |
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Abstract: | 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 Spo11 to catalyze meiotic DNA double-strand breaks (DSBs) at recombination hotspots. We found that the Schizosaccharomyces pombe Spo11 homolog Rec12 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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