Figure 1.

Schematic depiction of overlapping ATM role in DNA damage and oxidative stress response showing key molecules and cellular consequences. NRF2 activation could be ATM dependent or independent: ROS are able to directly activate NRF2 signaling via cysteine oxidation of NRF2 negative regulator KEAP1; indirect activation of NRF2 involves ATM-mediated block of NRF2 degradation. The role of p38 MAPK in NRF2 regulation remains to be fully elucidated (spotted line). p38 MAPK-mediated MK2 activation seems to be ATM-dependent (dashed line). ATR-mediated signaling is not activated in predominantly resting CLL cells and therefore is not shown in the figure.