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Digging into error control during DNA replication

The presence of ribonucleotides (rNTPs) in DNA can lead to genomic instability and cellular lethality. Adventitious rNTP incorporation is prevented during DNA polymerases copy activity through mechanisms that have been better understood using XRD2 structural data.

(Ref:  Johnson M. K. et al, NAR, 47(20), 10693–10705 (2019))

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.

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
Ultima modifica il Venerdì, 14 Febbraio 2020 16:58