Foldit puzzles don't normally involve DNA, but they may in the future. It's good to have the background.
There are four DNA "bases": Adenine, Cytosine, Guanine, and Thymine, usually known as ACGT. They form "base pairs" that span the famous double helix. Adenine can pair with Thymine, and Cytosine can pair with Guanine.
Foldit gives the pairs a color and a size. So the small yellow DNA base pairs with the large yellow DNA base. The small purple pairs with the large purple. The details are:
Still, the only valid pairings are AT, TA, CG, GC.
In this puzzle, Design Mode lets you "mutate" the DNA bases. Only the bases on the left helix can be mutated. There are three mismatched base pairs.
Make sure that the color of the base is the same on both strands of the helix, and that a large base on one side is paired with a small base on the other side. Click on the incorrect base and select the correct base from the DNA mutate wheel.