Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage
Abstract The genome of Corynebacterium pseudotuberculosis, etiologic agent of Caseous Lymphadenitis (CLA), was sequenced to comprehend its genetics, pathogenicity, and virulence mechanisms due to its economic importance. A focus was placed on the G/U mismatch-specific DNA glycosylase (Mug), an enzym...
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Sociedade Brasileira de Genética
2025-04-01
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| Series: | Genetics and Molecular Biology |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000200401&lng=en&tlng=en |
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| author | Bruno Carvalho Resende Cássio Siqueira Souza Cassiano Diego Lisboa Rios Thalia Queiroz Ladeira Vasco Ariston Carvalho Azevedo Luciana Lara dos Santos Lucía Valenzuela-Pérez Gonzalo Cabrera Carlos Renato Machado Débora de Oliveira Lopes |
| author_facet | Bruno Carvalho Resende Cássio Siqueira Souza Cassiano Diego Lisboa Rios Thalia Queiroz Ladeira Vasco Ariston Carvalho Azevedo Luciana Lara dos Santos Lucía Valenzuela-Pérez Gonzalo Cabrera Carlos Renato Machado Débora de Oliveira Lopes |
| author_sort | Bruno Carvalho Resende |
| collection | DOAJ |
| description | Abstract The genome of Corynebacterium pseudotuberculosis, etiologic agent of Caseous Lymphadenitis (CLA), was sequenced to comprehend its genetics, pathogenicity, and virulence mechanisms due to its economic importance. A focus was placed on the G/U mismatch-specific DNA glycosylase (Mug), an enzyme vital for base excision repair in DNA that can play an important role in uracil repair, since the high G+C content of C. pseudotuberculosis makes it prone to deamination events, accentuating the potential significance of Mug. Through in silico and in vitro analyses, the Corynebacterium pseudotuberculosis Mug protein (CpMug) was characterized to confirm its DNA glycosylase activity and lesion affinity. The mug gene was identified in both pathogenic and non-pathogenic Corynebacterium species, lacking a discernible ancestry pattern. Bioinformatics analyses revealed the preservation of essential uracil DNA glycosylase catalytic residues in CpMug. The 3D structure of CpMug was constructed, and molecular docking analysis demonstrated its interaction with DNA containing uracil and other lesions. Comparative analyses revealed a higher affinity of CpMug’s catalytic residues for uracil over other DNA lesions and enzymatic assays with purified CpMug affirmed its uracil DNA glycosylase activity, while it exhibited no activity on 8-oxoguanine, tetrahydrofuran, or thymine glycol, consistent with computational simulations. |
| format | Article |
| id | doaj-art-e306fd6ae30444ed86b06f5f5c7db279 |
| institution | OA Journals |
| issn | 1678-4685 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Sociedade Brasileira de Genética |
| record_format | Article |
| series | Genetics and Molecular Biology |
| spelling | doaj-art-e306fd6ae30444ed86b06f5f5c7db2792025-08-20T02:24:57ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852025-04-0148210.1590/1678-4685-gmb-2023-0353Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damageBruno Carvalho Resendehttps://orcid.org/0000-0001-6556-9773Cássio Siqueira Souza Cassianohttps://orcid.org/0000-0002-7525-8626Diego Lisboa Rioshttps://orcid.org/0000-0002-9065-7959Thalia Queiroz Ladeirahttps://orcid.org/0009-0005-6725-9919Vasco Ariston Carvalho Azevedohttps://orcid.org/0000-0002-4775-2280Luciana Lara dos Santoshttps://orcid.org/0000-0001-6186-4062Lucía Valenzuela-Pérezhttps://orcid.org/0000-0002-5145-303XGonzalo Cabrerahttps://orcid.org/0000-0002-1472-2608Carlos Renato Machadohttps://orcid.org/0000-0002-8724-3165Débora de Oliveira Lopeshttps://orcid.org/0000-0002-8559-8552Abstract The genome of Corynebacterium pseudotuberculosis, etiologic agent of Caseous Lymphadenitis (CLA), was sequenced to comprehend its genetics, pathogenicity, and virulence mechanisms due to its economic importance. A focus was placed on the G/U mismatch-specific DNA glycosylase (Mug), an enzyme vital for base excision repair in DNA that can play an important role in uracil repair, since the high G+C content of C. pseudotuberculosis makes it prone to deamination events, accentuating the potential significance of Mug. Through in silico and in vitro analyses, the Corynebacterium pseudotuberculosis Mug protein (CpMug) was characterized to confirm its DNA glycosylase activity and lesion affinity. The mug gene was identified in both pathogenic and non-pathogenic Corynebacterium species, lacking a discernible ancestry pattern. Bioinformatics analyses revealed the preservation of essential uracil DNA glycosylase catalytic residues in CpMug. The 3D structure of CpMug was constructed, and molecular docking analysis demonstrated its interaction with DNA containing uracil and other lesions. Comparative analyses revealed a higher affinity of CpMug’s catalytic residues for uracil over other DNA lesions and enzymatic assays with purified CpMug affirmed its uracil DNA glycosylase activity, while it exhibited no activity on 8-oxoguanine, tetrahydrofuran, or thymine glycol, consistent with computational simulations.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000200401&lng=en&tlng=enUracilG/U mismatch-specific DNA glycosylaseCorynebaterium pseudotuberculosisDNA repairbase excision repair |
| spellingShingle | Bruno Carvalho Resende Cássio Siqueira Souza Cassiano Diego Lisboa Rios Thalia Queiroz Ladeira Vasco Ariston Carvalho Azevedo Luciana Lara dos Santos Lucía Valenzuela-Pérez Gonzalo Cabrera Carlos Renato Machado Débora de Oliveira Lopes Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage Genetics and Molecular Biology Uracil G/U mismatch-specific DNA glycosylase Corynebaterium pseudotuberculosis DNA repair base excision repair |
| title | Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage |
| title_full | Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage |
| title_fullStr | Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage |
| title_full_unstemmed | Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage |
| title_short | Mismatch uracil DNA glycosylase (Mug) is maintained in the Corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage |
| title_sort | mismatch uracil dna glycosylase mug is maintained in the corynebacterium pseudotuberculosis genome and exhibits affinity for uracil but not other types of damage |
| topic | Uracil G/U mismatch-specific DNA glycosylase Corynebaterium pseudotuberculosis DNA repair base excision repair |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000200401&lng=en&tlng=en |
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