The uracil–DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID

Safavi, Sayyed Morteza; Larouche, Ariane; Zahn, Astrid; Patenaude, Anne-Marie; Domańska, Diana; Dionne, Kiersten; Rognes, Torbjørn; Dingler, Felix A.; Kang, Seong-Kwi; Liu, Yan; Johnson, Nathalie A.; Verdún, Ramiro E.; Rada, Cristina; Vega, Francisco; Nilsen, Hilde; Noia, Javier M. Di

doi:10.1093/narcan/zcaa045

Cited by 2 publications

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“…Gelsolin is an actin binding/severing protein involved in cardiac remodeling following myocardial infarction as is cathepsin L. , Both cyclin-dependent kinase 5 and ephrin type A-receptor 2-tyrosine kinase, which share strong pocket similarity, are associated with neuronal networking . Calgranulin and S adenosylmethionine decarboxylase β both play a significant role in inflammatory arthritis. , Uracil-DNA glycosylase and cathepsin L may play an antagonistic role in cancers. , Ras-related protein RAL-A and ephrin-type A receptor 3 are important in cancer progression . Caspase-3 is involved in apoptosis while fibrinogen α is involved in blood clotting. , By activating neutrophils, fibrinogen plays a role in delaying apoptosis .…”

Section: Resultsmentioning

confidence: 99%

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Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein–Protein Interactions

Skolnick

Zhou

2022

J. Phys. Chem. B

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Protein–protein interactions (PPIs) and protein–metabolite interactions play a key role in many biochemical processes, yet they are often viewed as being independent. However, the fact that small molecule drugs have been successful in inhibiting PPIs suggests a deeper relationship between protein pockets that bind small molecules and PPIs. We demonstrate that 2/3 of PPI interfaces, including antibody–epitope interfaces, contain at least one significant small molecule ligand binding pocket. In a representative library of 50 distinct protein–protein interactions involving hundreds of mutations, >75% of hot spot residues overlap with small molecule ligand binding pockets. Hence, ligand binding pockets play an essential role in PPIs. In representative cases, evolutionary unrelated monomers that are involved in different multimeric interactions yet share the same pocket are predicted to bind the same metabolites/drugs; these results are confirmed by examples in the PDB. Thus, the binding of a metabolite can shift the equilibrium between monomers and multimers. This implicit coupling of PPI equilibria, termed “metabolic entanglement”, was successfully employed to suggest novel functional relationships among protein multimers that do not directly interact. Thus, the current work provides an approach to unify metabolomics and protein interactomics.

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Section: Resultsmentioning

confidence: 99%

“… 72 , 73 Uracil-DNA glycosylase and cathepsin L may play an antagonistic role in cancers. 74 , 75 Ras-related protein RAL-A and ephrin-type A receptor 3 are important in cancer progression. 76 Caspase-3 is involved in apoptosis 77 while fibrinogen α is involved in blood clotting.…”

Section: Resultsmentioning

confidence: 99%

Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein–Protein Interactions

Skolnick

Zhou

2022

J. Phys. Chem. B

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“…Uracil's presence in DNA has been identified to be an important key intermediate in both adaptive and innate immunity (see Section 4.2). In adaptive immunity, U is introduced into DNA by the enzyme activation-induced deaminase (AID), where in B lymphocytes its presence modulates the antibody binding site or initiation of Ig isotype switching [29,30]. In innate immunity, U in DNA serves as an intermediate in the restriction of viral pathogens with the assistance of the family of APOBEC polynucleotide deaminases, where there is a C:U hypermutation of the viral genome leading to its degradation [31].…”

Section: Uracilmentioning

confidence: 99%

The Importance of the Fifth Nucleotide in DNA: Uracil

Roberts¹,

LaBonte²

2023

Oligonucleotides - Overview and Applications

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Uracil is a ribonucleotide found in both DNA and RNA, with the main difference between the two being the presence of thymine in DNA and uracil in RNA. Although thymine and uracil are similar in function and can form the same base pairs with adenine, the presence of uracil in DNA can affect DNA stability and modulate cell-specific functions. Without repair mechanisms to remove uracil from DNA, cytosine deamination can occur, resulting in gene drift that is not tolerable in organisms. While the deamination of cytosine in DNA signals damage, a corresponding deamination in RNA would yield normal RNA constituents. To correct this, uracil DNA glycosylases detect and remove uracil bases from uracil-containing DNA, but not natural thymine-containing DNA. The mechanisms of uracil incorporation into DNA, its roles in DNA, cellular mechanisms to detect and remove uracil, and the clinical utility of uracil in DNA will be discussed in this chapter.

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The uracil–DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID

Cited by 2 publications

References 0 publications

Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein–Protein Interactions

Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein–Protein Interactions

The Importance of the Fifth Nucleotide in DNA: Uracil

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