Bochman Lab
Every genome contains information that must be faithfully transmitted from one generation to the next to propagate life. Thus, maintaining genomic stability is crucial for biology, the importance of which is exemplified by the exquisite and often redundant regulation of all transactions involving DNA. Even more telling of the importance of genome integrity is the spectrum of problems that occur when stability is compromised. Genomic instability can be caused by metabolic byproducts, exogenous DNA damaging agents, and errors in DNA replication, recombination, and repair. More importantly, all of these genomic insults can result in tumorigenesis, premature aging, neurological disease, and cell death.
Ultimately, genomic stability hinges on proper DNA metabolism (i.e., high fidelity replication, recombination, repair, and telomere maintenance), and DNA helicases represent one of the major classes of enzymes involved in nearly all facets of these processes. Helicases are motor proteins that use the energy from nucleotide hydrolysis to unwind double-stranded DNA into single-stranded DNA. As both guardians and caretakers of the genome, organisms encode a diverse array of helicases (~30 in model prokaryotes and hundreds in model eukaryotes). However, despite 30 years of research since the discovery of the first helicases, the in vivo functions of many such enzymes remain unknown, despite the fact that mutations in many human helicases are linked to a variety of diseases involving genomic instability.
We are interested in the in vitro and in vivo characterization of diverse helicases from bacteria to humans, determining why their dysfunction often leads to disease states, and the evolution and specialization of the various enzymatic activities that helicases possess.