Figure 5
From: Cip/Kip cyclin-dependent protein kinase inhibitors and the road to polyploidy
Role of p21Cip1 in preventing apoptosis during endocycles. Upon completion of DNA replication in mitotic cell cycles, Cdc25 protein phosphatase and cyclin B are transported into the nucleus where they convert the inactive form of Cdk1 into an active form that can bind to cyclins and initiate mitosis. ATR is a protein kinase that senses the presence of excess single-stranded DNA resulting either from stalled replication forks, or from DNA damage. ATR then phosphorylates Chk1. This activates the Chk1 protein kinase and it, in turn, phosphorylates Cdc25, inhibiting it and thereby preventing cells from entering mitosis until the problem is corrected. p21 either directly or indirectly prevents expression of Chk1 protein. Under these conditions, cells do not trigger apoptosis in response to incomplete DNA synthesis or DNA damage.