RecQ DNA helicases are critical enzymes for the maintenance of genome integrity. Studies of RecQ helicases in model prokaryotic and eukaryotic systems have demonstrated their vital roles in DNA replication, recombination, and repair. RecQ proteins function as ATP-dependent motors that operate on an unparalleled breath of DNA substrates ranging from linear DNA duplexes to fork DNA and Holliday junction structures. However, the physical mechanisms by which RecQ helicases recognize and process this unparalleled breath of DNA substrates are largely unknown. Another key question is why humans have five different RecQ helicases, while other organisms such as bacteria and yeast have only one or two. Strikingly, mutations affecting three of the five human RecQ helicases cause distinct genetic diseases, all of which display high predisposition to cancer. The unique clinical features of these disorders support the notion that the different RecQ helicases have non-overlapping functions, but the molecular basis for their different enzymatic activities remains unclear. Our goal is to define the distinct molecular mechanisms of the five human RecQ helicases in genome maintenance.
Our current focus is to combine biochemical and structural approaches to determine the molecular mechanisms by which RecQ helicases link their ATPase, DNA binding, and DNA unwinding/branch migration functions to process central intermediates of DNA replication and repair.