scholarly journals Viruses with U-DNA: New Avenues for Biotechnology

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 875
Author(s):  
Kinga K. Nagy ◽  
Mikael Skurnik ◽  
Beáta G. Vértessy
Keyword(s):  
Protein Interactions ◽  
Excision Repair ◽  
Biotechnological Applications ◽  
Free Living ◽  
Uracil Dna Glycosylase ◽  
Cytosine Deamination ◽  
Base Editing ◽  
Induce Mutation ◽  
Dna Base ◽  
Living Organisms

Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA–protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.

scholarly journals Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA

2021 ◽  
Vol 8 ◽  
Author(s):  
Yixin Xie ◽  
Chitra B. Karki ◽  
Jiawei Chen ◽  
Dongfang Liu ◽  
Lin Li
Keyword(s):  
Electrostatic Interactions ◽  
Excision Repair ◽  
Computational Study ◽  
Interfacial Area ◽  
Binding Pocket ◽  
Dna Glycosylase ◽  
Uracil Dna Glycosylase ◽  
Cytosine Deamination ◽  
Binding Interface ◽  
Damaged Dna

Uracil-DNA glycosylase (UDG) is one of the most important base excision repair (BER) enzymes involved in the repair of uracil-induced DNA lesion by removing uracil from the damaged DNA. Uracil in DNA may occur due to cytosine deamination or deoxy uridine monophosphate (dUMP) residue misincorporation during DNA synthesis. Medical evidences show that an abnormal expression of UDG is related to different types of cancer, including colorectal cancer, lung cancer, and liver cancer. Therefore, the research of UDG is crucial in cancer treatment and prevention as well as other clinical activities. Here we applied multiple computational methods to study UDG in several perspectives: Understanding the stability of the UDG enzyme in different pH conditions; studying the differences in charge distribution between the pocket side and non-pocket side of UDG; analyzing the field line distribution at the interfacial area between UDG and DNA; and performing electrostatic binding force analyses of the special region of UDG (pocket area) and the target DNA base (uracil) as well as investigating the charged residues on the UDG binding pocket and binding interface. Our results show that the whole UDG binding interface, and not the UDG binding pocket area alone, provides the binding attractive force to the damaged DNA at the uracil base.

DNA base excision repair and nucleotide excision repair proteins in malignant salivary gland tumors

2021 ◽  
Vol 121 ◽  
pp. 104987
Author(s):  
Fernanda Aragão Felix ◽  
Leorik Pereira da Silva ◽  
Maria Luiza Diniz de Sousa Lopes ◽  
Ana Paula Veras Sobral ◽  
Roseana de Almeida Freitas ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Nucleotide Excision Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Salivary Gland Tumors ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Nucleotide Excision ◽  
Base Excision ◽  
Malignant Salivary Gland Tumors

scholarly journals Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

2021 ◽  
Vol 22 (5) ◽  
pp. 2698
Author(s):  
Vladimir Shafirovich ◽  
Nicholas E. Geacintov
Keyword(s):  
Excision Repair ◽  
Dna Lesions ◽  
Dna Templates ◽  
Circular Dna ◽  
Damage Sensing ◽  
Cell Extracts ◽  
Dna Base ◽  
Nucleotide Excision ◽  
Repair Pathways ◽  
Cellular Dna

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.

A Versatile DNA Nanochip for Direct Analysis of DNA Base-Excision Repair

2010 ◽  
Vol 49 (49) ◽  
pp. 9412-9416 ◽  
Author(s):  
Masayuki Endo ◽  
Yousuke Katsuda ◽  
Kumi Hidaka ◽  
Hiroshi Sugiyama
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Direct Analysis ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision
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