Mediators of homologous DNA pairing

Abstract

Homologous DNA pairing and strand exchange are at the core of homologous recombination. These reactions are promoted by a DNA-strand-exchange protein assembled into a nucleoprotein filament comprising the DNA-pairing protein, ATP, and single-stranded DNA. The catalytic activity of this molecular machine depends on control of its dynamic instability by accessory factors. Here we discuss proteins known as recombination mediators that facilitate formation and functional activation of the DNA-strand-exchange protein filament. Although the basics of homologous pairing and DNA-strand exchange are highly conserved in evolution, differences in mediator function are required to cope with differences in how single-stranded DNA is packaged by the single-stranded DNA-binding protein in different species, and the biochemical details of how the different DNA-strand-exchange proteins nucleate and extend into a nucleoprotein filament. The set of (potential) mediator proteins has apparently expanded greatly in evolution, raising interesting questions about the need for additional control and coordination of homologous recombination in more complex organisms.

Figure 1.

The figure shows the increasing evolutionary complexity within the group of homologous recombination accessory factors that contribute to the formation and stability of the DNA-strand-exchange protein nucleoprotein filament in the key model organisms. Main homologous recombination steps (resection [Symington 2014], coating with ssDNA-binding protein [S], loading of the DNA-strand-exchange protein [R], and strand invasion) are shown schematically. Phylogenetic relationships between homologous proteins are indicated with solid lines in cases of well-supported orthology or broken lines when the exact evolutionary relationship is uncertain; x indicates no close homolog in a fully sequenced genome. Because phage, bacterial, and archaeal homologous recombination accessory proteins do not show detectably sequence similarity and have likely evolved independently, they are displayed as separate domains. Proteins that most closely meet the “mediator” definition criteria are indicated in bold. ∼ indicates the ability to promote annealing of protein-coated ssDNA, shared by UvsY, RecO, and RAD52, which is a remarkable example of convergent evolution emphasizing the universal usefulness of this biochemical activity.