A sequence-dependent exonuclease activity from Tetrahymena thermophila

BACKGROUND: Telomere function requires a highly conserved G rich 3'- overhang. This structure is formed by 5'-resection of the C-rich telomere strand. However, while many nucleases have been suggested to play a role in processing, it is not yet clear which nucleases carry out this 5'-resection. RESULTS: We used biochemical purification to identify a sequence-dependent exonuclease activity in Tetrahymena thermophila cell extracts. The nuclease activity showed specificity for 5'-ends containing AA or AC sequences, unlike Exo1, which showed sequence-independent cleavage. The Tetrahymena nuclease was active on both phosphorylated and unphosphorylated substrates whereas Exo1 requires a 5'-phosphate for cleavage. CONCLUSIONS: The specificities of the enzyme indicate that this novel Tetrahymena exonuclease is distinct from Exo1 and has properties required for 3'-overhang formations at telomeres.