South Africa took three key Australian wickets in the evening session on day three to move into a commanding position in Brisbane.
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The Proteas started the evening session on 434-7 and the hosts were able to quickly wrap up the innings as South Africa finished on 450.
David Warner only lasted four overs before being dismissed by the pace of Dale Steyn thanks to a good catch at slip from Jacques Kallis.
Morne Morkel dismissed Robert Quiney and Ricky Ponting in two crucial overs but Michael Clarke (34*) and Ed Cowan (49*) guided the Australians to 111-3 at the close of play.