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Rosie O'Donnell and Andie MacDowell aren't the likeliest duo to stage a sister act.

Nevertheless, they do -- and quite effectively, too -- in "Riding the Bus With My Sister," a frequently bemusing yet dramatic and true new movie CBS airing at 9 tonight as the 224th Hallmark Hall of Fame presentation.

MacDowell portrays Rachel Simon, the author of the same-named book inspired by Rachel's challenging relationship with her developmentally disabled sibling (O'Donnell), left on her own when their father dies.

A fashion photographer for purposes of the movie, Rachel (a professor in real life) has kept a distance from the spirited Beth, but she reluctantly accepts that must change since Beth can't maintain her independent living without the at-home supervision their late dad provided. Rachel puts her career on hold and moves in with Beth, who is all too aware of the emotional divide between them. Helping to bridge the gap is the friendly driver (D.W. Moffett) of the city bus Beth takes regularly.

Directed by Oscar-winning actress Anjelica Huston and adapted by veteran TV-movie writer Joyce Eliason), the film also features Richard T. Jones ("Judging Amy") as Beth's boyfriend, who is as shy as she is gregarious.

Also an executive producer of the project, O'Donnell appreciates that playing Beth was "scary. That's the reason I left the show (O'Donnell's syndicated 1996-2002 talk show), because I felt I had accomplished everything within that venue that I could. It got to be about staying just for the money, and frankly, I was always in it for the art. I needed to try something that terrified me artistically, and this did."

O'Donnell realizes a part like Beth Simon is "a hard thing to pull off. When you see actors who do it brilliantly, like Sean Penn in 'I Am Sam,' you watch them with awe. When I read this book, I thought, 'If I was braver, I'd be in the movie.' Then I talked to the writer, and before I knew it, Anjelica Huston was directing the movie . . . and how do you say no to that?"

O'Donnell and MacDowell weren't strangers when they began filming "Riding the Bus With My Sister," since the "Four Weddings and a Funeral" actress had appeared on O'Donnell's talk show.

"She was so prepared; I think she nails this performance," MacDowell says. "Every day with her was a breathtaking experience, because she really 'got' Beth and made her very real and very believable for me. She put her heart and soul into it."

Still, O'Donnell believes MacDowell has the tougher of the two lead roles. MacDowell doesn't necessarily disagree, reasoning that Rachel "feels that she knows everything, and she doesn't realize that she's about to learn so much from someone who is handicapped. In the end, Rachel is the one who's really handicapped; that's the perspective I took it from, at least."

MacDowell met the real Rachel Simon and found her "a very interesting lady. Right after I finished the movie, I came home and my book club was reading the book, so I had sort of an insider's view in talking about it."

Conversely, O'Donnell didn't meet her real-life counterpart, reporting that "her sister and the other producers decided it might be a little bit much for her. We didn't want to disrupt her world too much."

O'Donnell adds that Rachel sat down with Beth "in a park and interviewed her on videotape for about 40 minutes. I watched that over and over, and I worked on playing Beth for a good six months before we started shooting."

Although MacDowell did an episode of "The Practice" and the 2001 HBO movie "Dinner With Friends," she usually leans toward big-screen projects such as "sex, lies and videotape," "Groundhog Day" and the current "Beauty Shop." She says "something of the caliber" of "Riding the Bus With My Sister" keeps TV work on her radar.

"Obviously, a lot of television projects don't have the substance of this material. Having Rosie O'Donnell and Anjelica Huston brings it up several more notches and makes it that much more interesting."

Starting May 29, O'Donnell also will appear in a three-episode arc on the Showtime series "Queer as Folk." While "Riding the Bus With My Sister" gives her room to inject much of her familiar persona, she maintains, "I really just tried to serve the story. I know that sounds corny, but I think people are more similar than everybody says. Between me and Beth, one of us has a few more filters for societal integration, but she's as content and happy and full a person as anyone."