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Brexit minister David Frost said on Saturday he was resigning with immediate effect, citing concerns over the "political direction" of Prime Minister Boris Johnson's government.
"It is disappointing that this plan has become public this evening and in the circumstances I think it is right for me to write to step down with immediate effect," Frost said in a letter to Johnson which was made public by the prime minister's office.
Frost, a supporter of Brexit, has led the attempts by London to re-open negotiations over the terms of Britain's exit from the European Union.
His departure is the latest in a string of setbacks for Johnson who on Thursday saw his Conservative Party lose a stronghold electoral seat.
The Prime Minister said on Friday he took personal responsibility for the loss of a Conservative stronghold in an election defeat that showed public dismay over a litany of scandals and stepped up pressure from mutinous lawmakers.
"Lord Frost tendered his resignation a week ago - but was persuaded to stay until January," the the Mail on Sunday newspaper reported.
The newspaper said Frost's departure had been prompted by the introduction of additional COVID measures, including Covid passes, a broader discontent with tax rises and the cost of 'net zero' environmental policies.
Frost, a supporter of Brexit, has led the attempts by London to renegotiate the terms of Britain's exit from the European Union.
Downing Street did not immediately respond to requests for comment.
GB News presenter and Northern Ireland’s former first minister Arlene Foster described Lord Frost’s resignation as “enormous”.
In a tweet, she said: “The resignation of Lord Frost from the Cabinet is a big moment for the Government but enormous for those of us who believed he would deliver for NI.”
Labour’s deputy leader Angela Rayner said the news represented “a Government in total chaos right when the country faces an uncertain few weeks”.
She tweeted: “@BorisJohnson isn’t up to the job. We deserve better than this buffoonery.”
Liberal Democrat foreign affairs spokesperson Layla Moran said: “This shock resignation is a sign of the chaos and confusion at the heart of this Conservative government.
“The rats are fleeing Boris Johnson’s sinking ship as he lurches from crisis to crisis.
“Even the Prime Minister’s once-loyal supporters are now abandoning him, just as lifelong Conservative voters are switching in their droves to the Liberal Democrats.
“At a time we need strong leadership to get us through the pandemic, we instead have a weak Prime Minister who has lost the support of his allies and the trust of the British people.”