homology models ( 27 , 31 ). Both Rec102 and
Top6B have long, helical arms that feed into
the Spo11 interface; our model predicts a dif-
ferent angle for this arm and contains a kink
that corresponds to a conserved sequence
motif EYPMVF 192 inSaccharomycesthat is
missing in both archaeal TopoVI and mam-
mals (fig. S17, D and E). Mutations in this re-
gion can suppressrec104conditional alleles
( 33 ), suggesting that this part of Rec102 is
important for integrating Rec104 function
into the Spo11 core complex.The highly conserved Rad51 protein, which is
central to DNA repair, carries out key reactions
during homologous recombination, and muta-
tions in human paralogs are associated with
Fanconi anemia and multiple types of cancer
( 34 ). Rad51 paralogs can be positive regulatorsHumphreyset al.,Science 374 , eabm4805 (2021) 10 December 2021 5 of 12
Fig. 3. Protein complexes involved in molecule transport, membrane translocation, and mitochondria.Bars and coloring as in Fig. 2. Full names for
proteins are in table S3. Membrane-spanning regions are annotated on Vtc1-Vtc4 and Sed5-Sft2. Top left: model of Vtc1-Vtc4 complex, with superimposed crystal
structure (PDB: 3G3Q, chain A) of the VTC4 (bright yellow) with phosphate bound (red balls).
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