The Nuclease CPS-6 Overcomes Autoinhibition by Interacting with wah-1 During Apoptosis in C. elegans

Apoptosis depends on multiple pathways to execute changes in the biochemistry and structure of the dying cell. Apoptotic DNA degradation is one such pathway that fragments the chromosomes, allowing them to be cleared from the debris of the dead cell. In C. elegans, apoptotic DNA degradation is also important to the highly reproducible pattern of cell killing that occurs during normal development. Regulation of apoptotic DNA degradation occurs by multiple mechanisms. My thesis recapitulates the finding that interaction between nucleases is important for their killing activity. Additionally, I will show that mutation of the glutamine 130 residue of CPS-6 to alanine or lysine activates CPS-6. cps-6 normally requires wah-1 to promote the cell killing and the proper timing of apoptosis. These CPS-6 Q130 mutants, however, can function independently of wah-1. These results also suggest that, during apoptosis, the primary function of wah-1 is to activate CPS-6.