a WRN helicase activity. WRN protein (3 nM, lane 2 and 6 nM, lane 3) was incubated with a forked DNA substrate for 15 min at 37°C. Reaction products were analyzed on a 12% native polyacrylamide gel. Lane 1 forked DNA substrate, lane 4 heat-denatured substrate. b WRN exonuclease activity on a 34 bp forked substrate. Reactions contained 4 or 8 nM WRN (lanes 2 or 3, respectively) and were incubated with 0.5 nM DNA substrate for 15 min at 37°C. Lane 1 DNA substrate. Products were heat-denatured for 5 min at 95°C, analyzed on a 14% denaturing polyacrylamide gel and visualized using a PhosphorImager