There and back again: new single-molecule insights in the motion of DNA repair proteins

Cellular DNA repair machines are constantly at work supporting the integrity of our genomes. Numerous proteins cooperate to form a complex and adaptive system dedicated to detection and timely processing of DNA damage. The molecular underpinnings of how these proteins locate and discriminate DNA lesions, match homologous sequences, mend the DNA and attend to a replication in distress are of a paramount biomedical importance, but in many cases remain unclear. Combined with more conventional tools, single-molecule biochemistry has been stepping in to address the age-old problems in the DNA repair field. This review will address new insights into diffusive properties of three DNA repair systems: I will discuss the emerging model of how MutS homologues locate and respond to mismatches in the dsDNA; the mechanism by which RAD52 promotes annealing of complementary DNA strands coated with ssDNA binding protein RPA; and how the nucleoprotein filament formed by RecA recombinase on ssDNA searches for homology within duplex DNA. These three distinct DNA repair factors exemplify the dynamic nature of cellular DNA repair machines revealed by single-molecule studies.