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WASHINGTON — Sen. John Ensign of Nevada, the subject of an ethics investigation related to his affair with the wife of a former top aide, announced Thursday evening that he was resigning, effectively ending the high-profile Senate inquiry that had already ruined his once-promising political career.

“It is with tremendous sadness that I officially hand over the Senate seat that I have held for eleven years,” Ensign, a Republican, said in a statement issued Thursday. “The turbulence of these last few years is greatly surpassed by the incredible privilege that I feel to have been entrusted to serve the people of Nevada.”

Republican Party operatives said Ensign’s resignation, which will happen May 3, would open the door to Nevada’s governor, Brian Sandoval, to appoint a Republican to fill out the rest of the Senate term, thereby increasing the chances that the party would hold on to what may be a hotly contested seat next year. One likely candidate is Rep. Dean Heller, a Republican House member already running for the job. Ensign had not been planning to run for re-election.

If Heller is appointed, he would be able to run as an incumbent, and by leaving the House he could also avoid some of the politically charged votes expected to occur there in the coming months.

The resignation marks the final chapter in the career of a politician who a few even thought might end in the White House but who instead got caught up in a particularly salacious Washington scandal. Ensign, 53, a veterinarian and former casino executive, had cast himself as a religious conservative and lived with other lawmakers in a Capitol Hill townhouse run by a religious group.

But in 2007 he began an affair with the wife of his best friend and most loyal aide, Doug Hampton. Once, the Ensigns and the Hamptons vacationed together. Their children were playmates, and the senator even encouraged his friends to come to Washington.

After learning of the affair in 2008, Hampton confronted the senator. Soon after, he and his wife were given $96,000 by the senator’s parents as a gift and he left the senator’s staff.

Humiliated, and struggling to make a living, Doug Hampton threatened to make the affair public. Senate ethics investigators have been examining whether Ensign then tried to buy his silence by using his office to help Hampton’s fledgling lobbying career. In a series of interviews with The New York Times in 2009, Hampton said the senator had pushed people to hire him, with the understanding that he would be able to influence Ensign.