Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and 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...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.718587/full |
| _version_ | 1831521486276395008 |
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| author | Yixin Xie Chitra B. Karki Jiawei Chen Dongfang Liu Lin Li Lin Li |
| author_facet | Yixin Xie Chitra B. Karki Jiawei Chen Dongfang Liu Lin Li Lin Li |
| author_sort | Yixin Xie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T20:02:02Z |
| format | Article |
| id | doaj.art-46feff50c4d148f9b07a56f40360273e |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-13T20:02:02Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-46feff50c4d148f9b07a56f40360273e2022-12-21T23:33:08ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-08-01810.3389/fmolb.2021.718587718587Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNAYixin Xie0Chitra B. Karki1Jiawei Chen2Dongfang Liu3Lin Li4Lin Li5Computational Science Program, University of Texas at El Paso, El Paso, TX, United StatesComputational Science Program, University of Texas at El Paso, El Paso, TX, United StatesComputer Science Program, Santa Monica College, Santa Monica, CA, United StatesDepartment of Computer Engineering, Rochester Institute of Technology, Rochester, NY, United StatesComputational Science Program, University of Texas at El Paso, El Paso, TX, United StatesDepartment of Physics, University of Texas at El Paso, El Paso, TX, United StatesUracil-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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.718587/fulluracil-DNA glycosylaseUDG enzymeDNA damageDNA repairbase excision repairfolding energy |
| spellingShingle | Yixin Xie Chitra B. Karki Jiawei Chen Dongfang Liu Lin Li Lin Li Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA Frontiers in Molecular Biosciences uracil-DNA glycosylase UDG enzyme DNA damage DNA repair base excision repair folding energy |
| title | Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA |
| title_full | Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA |
| title_fullStr | Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA |
| title_full_unstemmed | Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA |
| title_short | Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA |
| title_sort | computational study on dna repair the roles of electrostatic interactions between uracil dna glycosylase udg and dna |
| topic | uracil-DNA glycosylase UDG enzyme DNA damage DNA repair base excision repair folding energy |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.718587/full |
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