Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways
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 b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2698 |
| _version_ | 1797412674152169472 |
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| author | Vladimir Shafirovich Nicholas E. Geacintov |
| author_facet | Vladimir Shafirovich Nicholas E. Geacintov |
| author_sort | Vladimir Shafirovich |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:06:33Z |
| format | Article |
| id | doaj.art-f368f96e58524b619e6c78945c91d0e2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:06:33Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f368f96e58524b619e6c78945c91d0e22023-12-03T12:54:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225269810.3390/ijms22052698Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair PathwaysVladimir Shafirovich0Nicholas E. Geacintov1Chemistry Department, New York University, New York, NY 10003-5180, USAChemistry Department, New York University, New York, NY 10003-5180, USAThe 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.https://www.mdpi.com/1422-0067/22/5/2698DNA damagebase excision repairnucleotide excision repairoxidative stressreactive oxygen speciesguanine oxidation |
| spellingShingle | Vladimir Shafirovich Nicholas E. Geacintov Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways International Journal of Molecular Sciences DNA damage base excision repair nucleotide excision repair oxidative stress reactive oxygen species guanine oxidation |
| title | Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways |
| title_full | Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways |
| title_fullStr | Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways |
| title_full_unstemmed | Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways |
| title_short | Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways |
| title_sort | excision of oxidatively generated guanine lesions by competitive dna repair pathways |
| topic | DNA damage base excision repair nucleotide excision repair oxidative stress reactive oxygen species guanine oxidation |
| url | https://www.mdpi.com/1422-0067/22/5/2698 |
| work_keys_str_mv | AT vladimirshafirovich excisionofoxidativelygeneratedguaninelesionsbycompetitivednarepairpathways AT nicholasegeacintov excisionofoxidativelygeneratedguaninelesionsbycompetitivednarepairpathways |