4'C-modified nucleotides as chemical tools for investigation and modulation of DNA polymerase function

Abstract

DNA polymerases catalyze the entire biological DNA synthesis in DNA replication, repair and recombination. A DNA polymerase is presented with a pool of four structurally similar dNTPs from which it must select the sole correct substrate for incorporation into the growing DNA strand. The mechanisms how these remarkable enzymes achieve this tremendous task is a matter of ­current interest and intensive discussion. Valuable new insights into complex DNA polymerase selectivity mechanisms were gained through employment of 4'C-alkylated nucleotide analogues in ­functional enzyme studies. First investigations indicate that the 4'C-modified substrates are promising for the development of faithful methods for genome diagnostics.