Republican Sen. Olympia Snowe of Maine will retire rather than seek re-election this year, she says.
In a statement, Snowe said she was frustrated "that an atmosphere of polarization and 'my way or the highway' ideologies has become pervasive in campaigns and in our governing institutions."
Snowe is known as a moderate who sometimes sides with Democrats in the increasingly partisan environment of Washington politics.
Democrats currently hold a 53-47 majority in the Senate. But Democrats and the two independents who caucus with them are defending 23 of the 33 seats up for grabs in November.
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