If your choices are the following:
a. The squirrel, who ran in circles around the circumference of the tree, chattered angrily at the curious cat.
b. The squirrel who ran in circles around the circumference of the tree, chattered angrily at the curious cat.
c. The squirrel, who ran in circles around the circumference of the tree chattered angrily, at the curious cat.
d. The squirrel who ran in circles around the circumference of the tree chattered angrily, at the curious cat.
Then the answer is letter A. The comma should be put before and after the direct object. This will give emphasis and support the subject.