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Clayburgh joined the Charles Street Repertory Theater in Boston. She appeared in numerous Broadway productions in the 1960s, including The Rothschilds and Pippin. Clayburg made her screen debut in The Wedding Party, filmed in 1963 but not released until six years later. She was nominated for the Academy Award as Best Actress for 1978's An Unmarried Woman, for which she won the "Best Actress Award" at the Cannes Film Festival, and for 1979's Starting Over. She also received strong notices for her performance in I'm Dancing as Fast as I Can (which co-starred Geraldine Page).

Her other films include Portnoy's Complaint, Gable And Lombard (in which she portrayed screen legend Carole Lombard), Silver Streak, Semi-Tough, It's My Turn (in which she proves the snake lemma) , First Monday in October and La Luna, a controversial role in Bertolucci's critically panned film. This includes a scene in which her character masturbates her son in an attempt to help his heroin addiction. Television audiences know her from numerous roles in series and movies including The Practice and as Ally McBeal's mother. She received Emmy Award nominations for her work in the made-for-television movie Hustling in 1975 and for her guest appearance in the television series Nip/Tuck in 2005.

In 2006, she appeared on Broadway in Neil Simon's Barefoot in the Park with Patrick Wilson and Amanda Peet; she played Peet's mother, a role originated by the late Mildred Natwick. She also returned to the screen as a therapist's eccentric wife in the all-star ensemble dramedy Running With Scissors, an autobiographical tale of teenage angst and dysfunction based on the book by Augusten Burroughs and co-starring Annette Bening, Brian Cox, Joseph Fiennes, Evan Rachel Wood, Alec Baldwin and Gwyneth Paltrow. Her next role will be as Pat Nixon in the film Dirty Tricks, directed by Running With Scissors director Ryan Murphy. As of 2007, Clayburgh is one of the stars of the ABC television series Dirty Sexy Money, playing Leticia Darling.

(wikipedia.org)