All eastbound lanes of the bridge were closed because of a police investigation, with an estimated opening time possibly in the vicinity of 9 a.m., a spokesman said.
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The California Highway Patrol is advising motorists to take alternate routes out of the city.
San Francisco Municipal Railway buses on the 25 line, which goes to Treasure Island, are being held until the lanes open, according to Muni spokesman Paul Rose.
"We have an estimate of around 9 a.m. for the lanes to open, depending on the police investigation," Rose said.
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A Sig-alert was issued shortly after 4 a.m. this morning because of police activity, according to the CHP.
The lanes are closed just east of the Yerba Buena Island tunnel.