Model of RecA-Mediated Homologous Recognition

We consider theoretically the homology search between a long double-stranded DNA and a RecA-single-stranded DNA nucleofilament, emphasizing the polymeric nature of the search and the ability of double-stranded DNA to overcome the difference in pitch between itself and the nucleofilament by thermally activated stretching from the canonical $B$ state to the metastable, stretched $S$ state. Our analytical first-passage-time analysis agrees well with experimental data, predicts new dependencies on the intracellular fluid viscosity and ionic strength, and strongly suggests that initial homologous recognition involves a three base-pair seed.

Figure 1

In the global search, dsDNA comes into contact with the RecA-ssDNA nucleofilament by Rouse diffusion in the bacterium volume $R^3$. In this figure, we show $N_{\mathrm{R}\mathrm{e}\mathrm{c}\mathrm{A}}=5$ nucleofilaments.

Figure 2

After the global search brings a Kuhn step of dsDNA, shaded in the figure, in contact with its homologous counterpart on the RecA-ssDNA, a finer-scale local search occurs. For the contact to result in homologous recognition, a seed element (shown in the inset as 3 bp) of dsDNA must align itself with the homologous ssDNA sequence and stretch from the $B$ state to the $S$ state. The lengths $l_0$, $l_k$, and $l_s$ are defined in the text.