How does the presence of 7-deazaguanine in DNA affect the ability of human TLS polymerases to bypass DNA-protein cross-links (DPCs)?

Label:chem

Topic
7-deazaguanine is a modified guanine base used in this study to create stable DNA-protein cross-links (DPCs) that mimic the lesions formed by antitumor nitrogen mustards. These lesions are typically labile and unsuitable for structural and biological studies. The study investigates the ability of human translesion synthesis (TLS) polymerases to bypass DPCs conjugated to the 7-deazaguanine position of DNA.

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 presence of 7-deazaguanine in DNA allows for the creation of stable DPCs that can be used to study the bypass mechanism of TLS polymerases. Human TLS polymerases κ and ι can bypass small peptide DPCs (10-mer) conjugated to 7-deazaguanine with low efficiency but high fidelity, inserting the correct nucleotide (C) opposite the lesion. However, 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 is a critical factor in determining the ability of TLS polymerases to bypass these lesions.
Return to Home Chemical List
Knowledge you may be interested in
How does Acetobacter ghanensis JN01 biodegrade acetaldehyde? How does Acetobacter ghanensis JN01 biodegrade ethanol? What is the role of Acetobacter ghanensis JN01 in the biodegradation of ethanol and acetaldehyde? How does elastin-like polypeptides (ELPs) fusion improve the soluble expression of acetaldehyde lyase (ALS)? How do different cooling rates after fermentation affect yeast viability and acetaldehyde production in wine? How does nitrogen supplementation during fermentation influence yeast viability and acetaldehyde production in the post-fermentation phase of wine? How can the stability of boronic acid compounds be improved for agricultural applications? How do boronic acids and their derivatives function as fungicides in agriculture? What is the potential of boronic acid derivatization and activity in agrochemical discovery? How does BD11 affect the virulence traits of Candida albicans? What are the structural and functional implications of 7-deazaguanine in DNA-protein cross-links (DPCs)? How does the 7-deazaguanine position in DNA influence the efficiency and fidelity of nucleotide insertion by human TLS polymerases during translesion synthesis? What role does molecular dynamics (MD) simulation play in understanding the bypass of 7-deazaguanine DNA-peptide lesions by human TLS polymerases? What is the role of 7-deazaguanine (7DG) in the inhibition of human purine nucleoside phosphorylase (HsPNP)? How does 7-deazaguanine (7DG) bind to human purine nucleoside phosphorylase (HsPNP)? What is the inhibitory effect of 7-deazaguanine (7DG) on HsPNP enzyme activity? How does the presence of 7-deazaguanine (7DG) affect the conformation of HsPNP? What is the role of halide exchange in tuning the optoelectronic properties of MAPbBr3 single crystals? What are the kinetics of the halide exchange reaction in MAPbBr3 single crystals? How does the halide exchange reaction affect the crystal structure and optical properties of MAPbBr3?