New substrates of DNA polymerases

Bis-(2'-deoxynucleoside) 5',5'-tetraphosphates and bis-(2'-deoxynucleoside) 5',5'-triphosphates were shown to be a new type of substrate for several DNA polymerases of human, bacterial and viral origin. Their substrate properties depend both on their structure and on the nature of the enzyme. They are incorporated by both termini in correspondence with the template nucleotide program in the active center. The results obtained support the mechanism of their direct incorporation rather than prior hydrolysis to dNTP. The highest activity of these compounds was observed for HIV reverse transcriptase. The probable biological significance of the reaction is discussed.