DNA damage detection by DNA dependent protein kinase and related enzymes.

I have shown how the approaches of mammalian genetics, yeast molecular genetics and protein biochemistry have identified a series of related proteins that function in DNA repair and in DNA damage detection. The fact that one member of the family is a DNA damage activated protein kinase suggests how these factors might function in activating the DNA repair apparatus and in triggering DNA damage signalling pathways. Interestingly, several members of the family also have key roles in recombination--the best examples being provided by DNA-PK, which is essential for V(D)J recombination. Major goals for future research will be to determine precisely how DNA-PK and its relatives function at the molecular level and to identify and characterize other components of the DNA repair and DNA damage signalling pathways. Perhaps most significantly from the perspective of cancer research, however, defects in ATM lead to enhanced tumour incidence in the humans. This raises the exciting prospect that deficiencies in other members of the DNA-PKcs/ATM family will predispose individuals to cancer and that further research into this group of enzymes will provide important insights into the mechanisms of tumori-genesis.