Abstract: The effects of the amino, hydroxyl, imidazole and carboxyl groups of Ser-His on DNAcleavage reaction were studied.It was found that the amino and hydroxyl groups were essential for the DNAcleavage activity of Ser-His, and that anyone of them blocked would result into the loss of cleavage activity.The carboxyl group was not the necessary groupThe presence of the imidazole group would enhance the cleavage activity.However, the histidyl-serine dipeptide, as the formula isomer of Ser-His with the inverse peptide sequence, could not cleave DNAat all.Based on the above experimental results, a presumed cleavage mechanism of Ser-His on DNAwas proposed

Key words: Seryl-histidine dipeptide, Cleavage on DNA, Amino acids side chains effects, Cleavage mechanism