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Howard H. Baker Jr., the Republican senator from Tennessee who framed the question that cut to the heart of the official inquiry into the Watergate scandal, died Thursday, four days after a stroke. He was 88.

His death at his home in Huntsville, Tenn., was announced by a spokeswoman at his Memphis law firm, Baker Donelson, where he had been senior counsel.

A moderate Republican with bipartisan skill, Baker played many leading roles in his long government career, including White House chief of staff for President Ronald Reagan and later U.S. ambassador to Japan. But he was most famous for the one question he asked of witnesses during the 1973 Watergate hearings: “What did the president know, and when did he know it?”

The answers doomed the presidency of Richard M. Nixon and sealed Baker’s reputation as that rare find: a thoughtful politician who, as one reporter suggested, “had nothing at heart but the interests of our country.”

Baker initially believed in Nixon’s innocence but changed his mind as evidence accumulated of White House involvement in the June 17, 1972, break-in at the Democratic National Committee headquarters at the Watergate complex in Washington.

The Watergate hearings, televised live, wound up catapulting Baker to national attention, laying the groundwork for his presidential bid in 1980. But his role also drew the distrust of right-wing Republicans, who would never forgive him for contributing to the pressure that forced Nixon’s resignation.

The scion of a politically powerful family in Huntsville, Tenn.,Howard Henry Baker Jr. was born Nov. 15, 1925. His grandfather was a judge, his grandmother the first female sheriff in Tennessee. His father was a U.S. representative who served Tennessee’s 2nd District from 1951 until his death in 1964.

As a child, Baker excelled at debate and photography, two interests that would follow him into adulthood. He studied electrical engineering at the University of the South and at Tulane University. As a lieutenant in the Navy, he served briefly on a PT boat in the South Pacific before World War II ended.

After the war, he returned to college, this time at the University of Tennessee, where he studied law.

His first run for the Senate was in 1964, to fill the unexpired term of Democratic Sen. Estes Kefauver, who died in office.

Baker ran a conservative campaign, promising to limit foreign aid and federal interference in local education and civil rights, and lost to a more liberal candidate. Two years later, he ran again, this time taking more moderate positions – supporting, among other policies, fair-housing laws. He won with nearly 56 percent, cutting into the traditional Democratic vote and winning an unprecedented 35 percent of the black vote.

In 1976, according to news accounts, the Tennessee senator had hoped to get the vice presidential spot on Gerald R. Ford’s ticket, but that went instead to Sen. Robert Dole of Kansas. Baker sought the top spot himself in 1980, finishing third behind Reagan and George H.W. Bush in the New Hampshire primary.

So Baker remained in the Senate, where his instinct for compromise was rewarded. He was elected minority leader in 1977 and majority leader after the Reagan victory in 1980 swept the GOP into control of the Senate. But acrimony soon overcame his efforts at conciliation, and Baker opted not to seek re-election in 1984. Rep. Al Gore, a Democrat from another famous Tennessee political family, won the seat.

Baker prepared for a third run for the presidency in 1988, but let the White House know he was open to other high-ranking positions.

Then the Reagan White House suffered its most significant foreign policy crisis, an arms-for-hostages scandal in which weapons were sold to Iran in an effort to free American hostages held by militants in Lebanon – with the profits diverted to support rebels in Nicaragua, known as the contras. As the Iran-contra crisis consumed the White House, chief of staff Donald Regan resigned. Reagan asked Baker to become his chief of staff, and he helped Reagan begin the process of restoring trust in the White House.

“We were both extremely grateful that he agreed to take over the role of White House chief of staff during a very challenging time in 1987,” former first lady Nancy Reagan, who called Baker “one of Ronnie’s most valued advisers,” said in a statement Thursday.

Baker capped his career in 2001 when he was named ambassador to Japan. He served until 2005.