Linton Brooks became head of the agency in 2003
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US nuclear weapons agency chief Linton Brooks has been made to resign following a number of security breaches at Los Alamos Laboratory.
US Energy Secretary Samuel Bodman said new leadership at the National Nuclear Security Administration was needed.
"These management and security issues can have serious implications for the security of the US," Mr Bodman added.
The NNSA is in charge of maintaining the country's nuclear weapons stockpile and reducing the threat posed by WMDs.
The agency was created in 2000 after an espionage scandal at Los Alamos, site of US nuclear weapons research.
Mr Brooks became head of the agency in 2003 - two security lapses are known to have happened during his leadership.
In June last year, it emerged that a security breach which led to the theft of files containing information on more than 1,000 workers, had gone unreported for months.
Four months later, classified documents were found during a drugs raid on the home of a former Los Alamos employee.
Mr Brooks said in a statement he accepted the decision to remove him although "it was not a decision that I would have preferred".
"Our task is now to minimise the inevitable disruption of such a transition and to continue the vital national security work on which we are engaged," his statement added.
Mr Brooks is expected to leave the agency by the end of the month.