Biology Reference
In-Depth Information
F
IG
. 3. Exploiting synthetic lethal interactions for the treatment of human cancer. DNA
damage signaling networks commonly show extensive rewiring in tumor cells. (A) In p53- and
ATM-proficient (wt) cancer cells, DNA-damaging agents induce apoptosis. Conventional DNA-
damaging chemotherapy should be effective due to a functional proapoptotic ATM/Chk2-p53-
Puma/Noxa signaling pathway. (B) Loss-of-function mutations (mut) of
p53
in cancer cells largely
abrogate apoptosis induction in response to genotoxic stress. In these cells, ATM signaling induces a
robust cell cycle arrest, and ATM-mediated homologous recombination (HR) repair remains intact
