South Africa have lost five wickets for just 56 runs in the opening session on day three of the second Test.
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Peter Siddle has led the charge for Australia, leaving South Africa needing a further 74 runs to avoid the follow-on.
Siddle made the breakthrough early on when he dismissed Graeme Smith, who only managed to add 11 to his overnight score of 111. Smith called for a review but hot spot supported the decision of umpire Billy Bowden.
AB de Villiers was next to go, taken out lbw with just a single run to his name by a superb Siddle delivery.
Dale Steyn and Rory Kleinveldt fared little better for the visitors thanks a strong spell from Ben Hilfenhaus, who managed to take out Kleinveldt for a duck.
A middle-order collapse forced South Africa to send the injured Jacques Kallis to the crease.
Although clearly in pain Kallis has laid the foundations for a partnership with Faf du Plessis, who is 26 not out on his Test debut.