Inositol pyrophosphates are required for DNA hyperrecombination in protein kinase c1 mutant yeast

Diphosphoinositol pentakisphosphate (InsP(7)) and bis-diphosphoinositol tetrakisphosphate (InsP(8)) contain energetic pyrophosphate groups, occur throughout animal and plant kingdoms, and are synthesized by a recently cloned family of inositol hexakisphosphate kinases (InsP(6)Ks). We report that these inositol pyrophosphates mediate homologous DNA recombination in yeast S. cerevisae. Hyperrecombination, caused by altered protein kinase C1 (PKC1), is lost in yeast with deletion of yeast InsP(6)K (yInsP(6)K) and can be restored selectively by catalytically active yeast or mammalian InsP(6)Ks. Inositol pyrophosphates are required for two forms of hyperrecombination that differ in mechanism, suggesting some generalities for actions of inositol pyrophosphates in recombination.