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England claimed an 89-run lead on day three of the first Test after bowling South Africa out for 214 in Durban.
Stuart Broad struck with the second delivery of the morning, spinner Moeen Ali added three wickets and Steven Finn wrapped things up just before lunch with the new ball.
Opener Dean Elgar carried his bat for the Proteas, finishing with more than his 10 team-mates combined on 118 not out.
England will now look to build a sizeable lead and move into a winning position on a wearing Kingsmead pitch.
With the scoreboard resuming at 137 for four, Broad made an immediate breakthrough for England for the second day in a row.
On day two Stiaan van Zyl fell to the second ball of the day and this time Temba Bavuma shared that fate.
It was a modest delivery, hung outside off stump and keeping a touch low. But Bavuma's limp stroke, and the resulting under edge into leg stump, did not reflect well on the batsman.
South Africa desperately needed someone to stick with Elgar, who started with 67 from 155 balls.
He again looked compact and cautious but lost his next two partners in quick succession to Moeen's off spin.
By now the the all-rounder was getting considerable grip off a wearing pitch and neither JP Duminy nor Kyle Abbott were able to keep him out.
Moeen picked off the left-handed Duminy in time-honoured fashion - pitching a little outside middle, flicking the edge and landing gently in Ben Stokes' hands at slip.
Abbott looked even simpler prey for Moeen and the only surprise when he popped a bat-pad catch to James Taylor at short-leg was that Rod Tucker did not see it.
England, who missed the chance to review two potential dismissals on Sunday, did not hesitate this time and replays gave both Abbott and Tucker reason to blush.
Elgar continued to hold up the charge, punching Steven Finn down the ground to overtake Nick Compton's 85 as the highest score of the match.
Dale Steyn succeeded in blocking up the other end and Elgar brought up his hundred by flicking Joe Root's part-time spin off his pads for three.
With Broad lying in wait for the new ball, Elgar and Steyn, who had come together at 156 for seven, steered the score past 200.
The change of ball was two overs away when Steyn lost his cool and slogged Moeen high towards mid-off where Chris Woakes eventually held on after a couple of juggles.
Dane Piedt and Morne Morkel both succumbed in Finn's first over with the new ball to send England to the break in the ascendance.