New cell or new cycle?

In mammals, trophoblast giant (TG) cell differentiation is characterized by a physiological endoreduplication, resulting in genome size augmentation. A recent study by Ullah and colleagues (pp. 3024-3036), published in this issue of Genes & Development, now elucidates the role of the cyclin-dependent kinase inhibitors (CKIs), p21 and p57, in mammalian endocycle regulation.