Single-Molecule Analysis of Bacterial DNA Repair and Mutagenesis

Abstract

Ubiquitous conserved processes that repair DNA damage are essential for the maintenance and propagation of genomes over generations. Then again, inaccuracies in DNA transactions and failures to remove mutagenic lesions cause heritable genome changes. Building on decades of research using genetics and biochemistry, unprecedented quantitative insight into DNA repair mechanisms has come from the new-found ability to measure single proteins in vitro and inside individual living cells. This has brought together biologists, chemists, engineers, physicists, and mathematicians to solve long-standing questions about the way in which repair enzymes search for DNA lesions and form protein complexes that act in DNA repair pathways. Furthermore, unexpected discoveries have resulted from capabilities to resolve molecular heterogeneity and cell subpopulations, provoking new questions about the role of stochastic processes in DNA repair and mutagenesis. These studies are leading to new technologies that will find widespread use in basic research, biotechnology, and medicine.