BEIRUT — A suicide bomber struck the National Security building in the Syrian capital today, killing the defense minister and President Bashar Assad’s brother-in-law — the harshest blow to the Syrian regime since the uprising began.

Syrian state-run TV said the blast came during a meeting of Cabinet ministers and senior security officials in Damascus, where four straight days of clashes pitting government troops against rebels have sent tensions soaring.

Defense Minister Dawoud Rajha, 65, a former army general, was the most senior government official to be killed in the Syrian civil war as rebels battle to oust Assad. Gen. Assef Shawkat, the deputy defense minister and one of the most feared figures in Assad’s inner circle, also was killed. He was married to Assad’s older sister, Bushra.

Interior Minister Mohammed Shaar was wounded and in stable condition, state TV said.

Republican Guard troops surrounded the nearby al-Shami Hospital, where some officials were taken for treatment, witnesses said.

The Assad family has ruled Syria for four decades, creating an ironclad and impenetrable regime. Today’s attack was a nearly unheard-of strike on the inner circle.

Although it was unclear who was behind the attack, the high-level assassinations could signal a turning point in the 16-month conflict.