How does the 7-deazaguanine position in DNA influence the efficiency and fidelity of nucleotide insertion by human TLS polymerases during translesion synthesis?

Label:chem

Topic
The study investigates the efficiency and fidelity of nucleotide insertion opposite DNA-peptide lesions conjugated to the 7-deazaguanine position in DNA. The lesions are modeled using 10-mer and 23-mer peptides.

From: "Bypass of DNA-Protein Cross-links Conjugated to the 7-Deazaguanine Position of DNA by Translesion Synthesis Polymerases", JBC, Volume 291, Issue 45, November 2016, Pages 23589-23603
Answer
The 7-deazaguanine position in DNA allows for the creation of stable DPCs that can be used to study the efficiency and fidelity of nucleotide insertion by human TLS polymerases. The study shows that human TLS polymerases κ and ι can insert nucleotides opposite the 10-mer peptide lesion with high fidelity, preferentially incorporating the correct base (C). However, the efficiency of nucleotide insertion opposite the 10-mer peptide lesion is significantly lower than for native guanine. The 23-mer peptide lesion blocks replication in standing start experiments but allows partial bypass under running start conditions, indicating that the size of the peptide conjugated to 7-deazaguanine affects the ability of TLS polymerases to bypass the lesion.
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