While both SCF–Skp2 and PCNA–Cul4–Ddb1–Cdt2 mediate degradation of Cdt1 in S phase redundantly, Nishitani et al. legantly demonstrated the distinct functions of these pathways during the cell cycle. Utilizing Cdt1 mutants specifically defective for SCF–Skp2 binding (Cdt1 Cy motif mutant) and for Cul4– Ddb1–Cdt2 association (Cdt1 PIP motif mutant) in cells synchronized for early , mid-S, and G2, they showed that Cul4–Ddb1– Cdt2 functions to degrade Cdt1 only in S phase, whereas SCF–Skp2 acts in both S and G2