What are the structural and functional implications of 7-deazaguanine in DNA-protein cross-links (DPCs)?

Label:chem

Topic
7-deazaguanine is used in this study to create stable DPCs that resemble lesions induced by antitumor nitrogen mustards. These lesions are typically hydrolytically labile, making them difficult to study. The study investigates the structural and functional implications of 7-deazaguanine in DPCs and their impact on DNA replication.

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 use of 7-deazaguanine in DPCs allows for the creation of stable lesions that can be studied in vitro. The study shows that small peptide DPCs (10-mer) conjugated to 7-deazaguanine can be bypassed by human TLS polymerases κ and ι with high fidelity, although with reduced efficiency compared to native guanine. Larger DPCs (23-mer peptides and full-length proteins) completely block DNA replication. The study suggests that the size of the peptide or protein conjugated to 7-deazaguanine significantly affects the ability of TLS polymerases to bypass these lesions, with smaller peptides allowing for more efficient bypass.
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