Mammalian endoreplication emerges to reveal a potential developmental timer

a The three main cell products of endoreplication upon: endoreduplication, a single polyploid nucleus; endomitosis, a lobulated polyploid nucleus; and acytokinetic mitosis, two (or more) nuclei. b The cyclin switch driving proliferation into endoreplication. During endoreplication, expression of Cyclin B or Cyclin A ceases, while expression of Cyclin E is maintained. c The G2 or mitosis checkpoints block cell division and induce endoreplication in response to irreparable DNA damage caused by cell cycle stress, for instance, upon ectopic Cyclin E. The DDDR triggers differentiation, thus suppressing cell divison. In keratinocytes, overexpression of the global mitotic regulator FoxM1 allows damaged cells to continue to divide, thus promoting genomic instability. References within the main tex