We investigate to what extent the recently measured value for a non-vanishing direct CP asymmetry in D0 -> K+ K- and D0 -> pi+ pi- decays can be accommodated in the Standard Model (SM) or extensions with a constrained flavour sector, for instance from a sequential 4th generation of quarks (4G). From the comparison with D0 -> K- pi+ branching ratios, we establish large U-spin symmetry (d <-> s) breaking effects with large strong phases between different interfering amplitudes. On the basis of conservative estimates on amplitude ratios - which are supported by an analysis of the breaking of a (c <-> u) symmetry in non-leptonic B0 decays - we find that, in the SM, direct CP asymmetries in the pi+ pi- or K+ K- modes (or in their difference) of the order of several per mille are still plausible. Due to the constraints on the new CP phases in the 4G model, only moderate effects compared to the SM estimates are possible. We suggest CP studies at LHCb as well as at (Super)B-factories of several distinctive modes, such as D+ -> Kbar(*)0 pi+, phi pi+ and Ds -> K(*)0 pi+, phi pi+ (K+) etc., which should shed more light on the short- and long-distance issues underlying CP violation in non-leptonic D-meson decays.
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