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.

scholarly journals Embryonic extracts derived from the nematode Caenorhabditis elegans remove uracil from DNA by the sequential action of uracil-DNA glycosylase and AP (apurinic/apyrimidinic) endonuclease

2002 ◽  
Vol 365 (2) ◽  
pp. 547-553 ◽  
Author(s):  
Andrea SHATILLA ◽  
Dindial RAMOTAR
Keyword(s):  
Caenorhabditis Elegans ◽  
Excision Repair ◽  
Specific Inhibitor ◽  
Dna Glycosylase ◽  
Dependent Manner ◽  
Nematode Caenorhabditis Elegans ◽  
Uracil Dna Glycosylase ◽  
Ap Endonuclease ◽  
C Elegans ◽  
Ap Site

DNA bases continuously undergo modifications in response to endogenous reactions such as oxidation, alkylation or deamination. The modified bases are primarily removed by DNA glycosylases, which cleave the N-glycosylic bond linking the base to the sugar, to generate an apurinic/apyrimidinic (AP) site, and this latter lesion is highly mutagenic. Previously, no study has demonstrated the processing of these lesions in the nematode Caenorhabditis elegans. Herein, we report the existence of uracil-DNA glycosylase and AP endonuclease activities in extracts derived from embryos of C. elegans. These enzyme activities were monitored using a defined 5′-end 32P-labelled 42-bp synthetic oligonucleotide substrate bearing a single uracil residue opposite guanine at position 21. The embryonic extract rapidly cleaved the substrate in a time-dependent manner to produce a 20-mer product. The extract did not excise adenine or thymine opposite guanine, although uracil opposite either adenine or thymine was processed. Addition of the highly specific inhibitor of uracil-DNA glycosylase produced by Bacillus subtilis to the extract prevented the formation of the 20-mer product, indicating that removal of uracil is catalysed by uracil-DNA glycosylase. The data suggest that the 20-mer product was generated by a sequential reaction, i.e., removal of the uracil base followed by 5′-cleavage of the AP site. Further analysis revealed that product formation was dependent upon the presence of Mg2+, suggesting that cleavage of the AP site, following uracil excision, is carried out by a Mg2+-dependent AP endonuclease. It would appear that these activities correspond to the first two steps of a putative base-excision-repair pathway in C. elegans.

Is Uracil-DNA Glycosylase UNG2 a New Cellular Weapon Against HIV-1?

2019 ◽  
Vol 17 (3) ◽  
pp. 148-160 ◽  
Author(s):  
Hesna Kara ◽  
Nathalie Chazal ◽  
Serge Bouaziz
Keyword(s):  
Excision Repair ◽  
Repair Process ◽  
Replication Cycle ◽  
Dna Glycosylase ◽  
Uracil Dna Glycosylase ◽  
Double Stranded Dna ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Negative Role ◽  
Hiv 1

Uracil-DNA glycosylase-2 (UNG2) is a DNA repair protein that removes uracil from single and double-stranded DNA through a basic excision repair process. UNG2 is packaged into new virions by interaction with integrase (IN) and is needed during the early stages of the replication cycle. UNG2 appears to play both a positive and negative role during HIV-1 replication; UNG2 improves the fidelity of reverse transcription but the nuclear isoform of UNG2 participates in the degradation of cDNA and the persistence of the cellular genome by repairing its uracil mismatches. In addition, UNG2 is neutralized by Vpr, which redirects it to the proteasome for degradation, suggesting that UNG2 may be a new cellular restriction factor. So far, we have not understood why HIV-1 imports UNG2 via its IN and why it causes degradation of endogenous UNG2 by redirecting it to the proteasome via Vpr. In this review, we propose to discuss the ambiguous role of UNG2 during the HIV-1 replication cycle.

scholarly journals SMUG2 DNA glycosylase from Pedobacter heparinus as a new subfamily of the UDG superfamily

2017 ◽  
Vol 474 (6) ◽  
pp. 923-938 ◽  
Author(s):  
Panjiao Pang ◽  
Ye Yang ◽  
Jing Li ◽  
Zhong Wang ◽  
Weiguo Cao ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Excision Repair ◽  
Phylogenetic Analyses ◽  
Dna Glycosylase ◽  
Amino Acid Residues ◽  
Uracil Dna Glycosylase ◽  
Important Amino Acid ◽  
Repair Mechanisms ◽  
Ap Sites ◽  
Base Excision

Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are essential to maintain genome integrity, in which the base excision repair (BER) pathway plays a major role in the removal of base damage. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for excising the deaminated bases from DNA and generates apurinic/apyrimidinic (AP) sites. Using bioinformatics tools, we identified a family 3 SMUG1-like DNA glycoyslase from Pedobacter heparinus (named Phe SMUG2), which displays catalytic activities towards DNA containing uracil or hypoxanthine/xanthine. Phylogenetic analyses show that SMUG2 enzymes are closely related to family 3 SMUG1s but belong to a distinct branch of the family. The high-resolution crystal structure of the apoenzyme reveals that the general fold of Phe SMUG2 resembles SMUG1s, yet with several distinct local structural differences. Mutational studies, coupled with structural modeling, identified several important amino acid residues for glycosylase activity. Substitution of G65 with a tyrosine results in loss of all glycosylase activity. The crystal structure of the G65Y mutant suggests a potential misalignment at the active site due to the mutation. The relationship between the new subfamily and other families in the UDG superfamily is discussed. The present study provides new mechanistic insight into the molecular mechanism of the UDG superfamily.

scholarly journals Uracil-DNA Glycosylase in Base Excision Repair and Adaptive Immunity

2011 ◽  
Vol 286 (19) ◽  
pp. 16669-16680 ◽  
Author(s):  
Berit Doseth ◽  
Torkild Visnes ◽  
Anders Wallenius ◽  
Ida Ericsson ◽  
Antonio Sarno ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Glycosylase ◽  
Uracil Dna Glycosylase ◽  
Base Excision
Sign in / Sign up

Export Citation Format

Share Document