Figure 1. ATM inactivation overcomes replication stress-induced senescence.

In cells with functional ATM, replication stress induces senescence. In cells without ATM, there is a coordinated upregulation of c-MYC and downregulation of p53 to increase glucose and glutamine utilization. Additionally, decreased p53 increases activity of the pentose phosphate pathway (PPP). This reprogramming in cellular metabolism increases dNTPs, which allows for cells to overcome the senescence-associated cell growth arrest to proliferate.