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Pakistan, striving to save the second Test, were 56 for three at tea after South Africa piled up a big 418-run lead on the third day in Dubai on Friday.
Pakistan lost both their openers without scoring and Azhar Ali for 19, before Younis Khan (29) and Misbah-ul Haq (seven) took them to tea.
South Africa made 517 in their first innings after resuming on 406 for four.
Pakistan trail by 362 runs with seven wickets in hand and two full days and a session to play.
Graeme Smith made 234 and AB de Villiers scored 164. For Pakistan off-spinner Saeed Ajmal finished with 5-161 and Mohammad Irfan took 3-102.
Pakistan lead the two-match series 1-0.