The absence of the 54-year-old actress from the drama will be difficult for the show's writers to overcome as Wettig's character was last seen taking over the U.S. presidency through dubious means in the season two-finale, TV Guide reported.
Instead the former "thirtysomething" star will join her husband, producer and writer Ken Olin, on the set of the new ABC TV series "Brothers & Sisters."
"I had to make a choice, and it was kind of hard for me to choose against my husband and his good writing," Wettig said during an appearance at the Television Critics Association summer press tour.
No details have been given regarding how "Prison Break" writers will deal with the actress' departure from the cast, TV Guide said.
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