Biology Reference
In-Depth Information
F
IG
. 1. DNA damage signaling, checkpoint control, and the role of p53. (A) DNA damage
signaling pathways. In response to genotoxic stress by chemotherapeutic agents, cells activate
complex signaling networks that control DNA repair and cell cycle arrest or initiate apoptosis if
the damage is extensive. DNA double-strand breaks (DSBs) primarily activate ATM, which in turn
phosphorylates its downstream effectors Chk2 and p53. Induction of cell cycle-regulatory p53
target genes like
p21
or
Gadd45
results in cell cycle arrest, while the activation of proapoptotic p53
a
