Kagiso Rabada claimed seven England wickets to leave South Africa in pole position by close of play on day three of the fourth Test in Centurion.
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Alastair Cook and Joe Root resumed their partnership at the crease chasing a deficit of 337 runs at the start of the day's action and Root soon notched his half-century.
The captain was the first of the day to fall, going out for 76 to Quinton de Kock after a strong delivery from Morne Merkel. Root followed suit by the same score as lunch approached, Rabada claiming his first wicket of the day and his third of the match to add to the dismissals of Alex Hales and Nick Compton on Saturday.
Another two wickets quickly followed before the break as James Taylor went out for 11 and under-fire Jonny Bairstow went on the third ball after failing to add to the tally.
Ben Stokes looked impressive after a rain delay extended lunch, taking five fours and a six from his first 29 balls but Rabada again claimed a major scalp as Stokes returned to the pavilion with a total of 33.
Chris Woakes's contribution of 26 ensured that England avoided the follow-on as Moeen Ali kept the fight alive until tea. Stuart Broad was the next to go, adding five from 18 balls as Rabada celebrated his seventh wicket, before Ali fell for 61 to end the session and leave the tourists 133 runs short.
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The second innings got off to a fine start for England as Jimmy Anderson claimed the scalp of Dean Elgar for 1, but Hashim Amla and Stephen Cook put on a firm stand to leave the Proteas 42-1 before bad light ended play.