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Mary McDonnell was renowned for her stage work on the East Coast, working with the Long Wharf Theatre Co., among others. Working in the theater for over 20 years, it was not until 1990 that she had her breakthrough film role in Kevin Costner's Dances With Wolves, for which she received an Academy Award nomination for Best Supporting Actress. Her role in Passion Fish (1992) brought her another Academy Award nomination, this time for Best Actress .
Other notable films include Grand Canyon (1991), Sneakers (1992), Independence Day (1996) and Donnie Darko (2001). In Donnie Darko, she played Mrs. Rose Darko, Donnie's mother. In Independence Day she played the dying first lady.
She is married to actor Randle Mell. Mell and McDonnell have two children, Olivia and Michael.