The central axis of the famous DNA double helix is often constrained or even circular. The topology of this axis can influence which proteins interact with the underlying DNA. Subsequently, in all cells there are proteins whose primary function (type II topoisomerases) is to change the DNA axis topology -- for example converting a torus link into an unknot. Additionally, there are several protein families (most importantly, site-specific recombinases) that change the axis topology as a by-product of their interaction with DNA. This talk will describe some typical DNA conformations, and the families of proteins that change these conformations. I'll present a few examples illustrating how 3-manifold topology (including Dehn surgery and Heegaard Floer homology) have been useful in understanding certain DNA-protein interactions, and discuss the most common techniques used to attack these problems.