Machines on Genes: A Single-Molecule Perspective

Faithful inheritance and precise expression of genetic information—fundamental to all forms of life—are carried out by specialized macromolecular machines. These nanometer-scale entities are constantly negotiating the physical characteristics and topology of DNA. In eukaryotes, the genome-associated machines face the additional challenge posed by nucleosome wrapping and chromatin compaction. How DNA- and chromatin-based machines navigate hierarchically organized chromosomes to access, modify, and decode the genome remains a major question in biology. In this talk, I will describe the research program developed in my laboratory that employs single-molecule biophysical methods to visualize and manipulate the behavior of protein machines on DNA and chromatin. I will present a few case studies to illustrate how our approach can provide new insight into the operating mechanisms of genetic and epigenetic machines on a crowded and heterogeneous genome.