DNA polymerases (dPols) possess two safety checks during genome replication. The first one, known as the steric filter, is composed of a bulky aliphatic or aromatic side chain that is present underneath the ribose sugar and will clash with the 2′-OH of the rNTP molecule to reduce the chances of it occupying the active site in a conformation compatible with productive catalysis. The present study shows the existence of a second polar filter, which interacts with the 3′-OH and triphosphate moiety of the incoming nucleotide and orients it closer to the surface of the fingers domain. X-ray structural studies provided structural insights into how dPol enzymes avoid incorporation of RNA nucleotides in DNA, using XRD2 data.
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Retrieve Article A polar filter in DNA polymerases prevents ribonucleotide incorporation, Mary K Johnson, Jithesh Kottur and Deepak T Nair Nucleic Acids Research 2019 47(20), 10693–10705, doi: 10.1093/nar/gkz792, PDB: 6JUN |