Fig. 1: DNA strand displacement topologies, catalysis mechanism of the template and system design.
a, TMSD. Binding to the toehold (t) domain in the target DNA strand (R) mediates displacement of the incumbent (C) by the invader (I). After displacement, the toehold is cooperatively sequestered in duplex IR. b, HMSD. When I binds to the handhold (h) domain in C, the effective concentration of I increases in the vicinity of R, enhancing displacement. The reversible nature of handhold binding allows IR to detach. c, The DNA-based catalytic templating system. The DNA monomers (MxL and Ny) can dimerize after binding to a DNA template (Txy), exploiting first toehold exchange (a TMSD variant) then HMSD. Dimerization between the monomers weakens the interaction with Txy, allowing MxNy to detach and for Txy to undergo another dimerization cycle. d, The specific-sequence domains of Txy can trigger the dimerization of a specific MxL, Ny pair from pools of monomers in solution. The result is a product distribution enriched in MxNy dimers with t and h domains (red boxes) complementary to Txy, propagating the sequence information in the template. Any x,y combination is possible, with the dimerization domain a initially hidden by L, inhibiting any direct reaction in the absence of Txy. The edges of the MxL duplex have additional bases—‘clamps’—suppressing any leak reactions. The two mismatched base pairs in the a domain of MxL ensure that dimerization is thermodynamically favoured. The DNA strands are represented by domains (contiguous sequences of nucleotides considered to hybridize as a unit). The domains are labelled with a lowercase letter; a prime symbol indicates complementarity; for example, a′ binds to a.
