Mice with a complete deficiency of p73 have severe neurological and 
immunological defects due to the absence of all TAp73 and DeltaNp73 isoforms. As 
part of our ongoing program to distinguish the biological functions of these 
isoforms, we generated mice that are selectively deficient for the DeltaNp73 
isoform. Mice lacking DeltaNp73 (DeltaNp73(-/-) mice) are viable and fertile but 
display signs of neurodegeneration. Cells from DeltaNp73(-/-) mice are 
sensitized to DNA-damaging agents and show an increase in p53-dependent 
apoptosis. When analyzing the DNA damage response (DDR) in DeltaNp73(-/-) cells, 
we discovered a completely new role for DeltaNp73 in inhibiting the molecular 
signal emanating from a DNA break to the DDR pathway. We found that DeltaNp73 
localizes directly to the site of DNA damage, can interact with the DNA damage 
sensor protein 53BP1, and inhibits ATM activation and subsequent p53 
phosphorylation. This novel finding may explain why human tumors with high 
levels of DeltaNp73 expression show enhanced resistance to chemotherapy.