Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids
Trypanosomatids are a group of primitive unicellular eukaryotes that can cause diseases in plants, insects, animals, and humans. Kinetoplast genome integrity is key to trypanosomatid cell survival and viability. Kinetoplast DNA (kDNA) is usually under attack by reactive oxygen and nitric species (RO...
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| Format: | Article |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.670564/full |
| _version_ | 1818356685703479296 |
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| author | Edio Maldonado Sebastian Morales-Pison Fabiola Urbina Aldo Solari |
| author_facet | Edio Maldonado Sebastian Morales-Pison Fabiola Urbina Aldo Solari |
| author_sort | Edio Maldonado |
| collection | DOAJ |
| description | Trypanosomatids are a group of primitive unicellular eukaryotes that can cause diseases in plants, insects, animals, and humans. Kinetoplast genome integrity is key to trypanosomatid cell survival and viability. Kinetoplast DNA (kDNA) is usually under attack by reactive oxygen and nitric species (ROS and RNS), damaging the DNA, and the cells must remove and repair those oxidatively generated lesions in order to survive and proliferate. Base excision repair (BER) is a well-conserved pathway for DNA repair after base damage, single-base loss, and single-strand breaks, which can arise from ROS, RSN, environmental genotoxic agents, and UV irradiation. A powerful BER system has been described in the T. cruzi kinetoplast and it is mainly carried out by DNA polymerase β (pol β) and DNA polymerase β-PAK (pol β-PAK), which are kinetoplast-located in T. cruzi as well as in other trypanosomatids. Both pol β and pol β-PAK belong to the X-family of DNA polymerases (pol X family), perform BER in trypanosomatids, and display intrinsic 5-deoxyribose phosphate (dRP) lyase and DNA polymerase activities. However, only Pol β-PAK is able to carry out trans-lesion synthesis (TLS) across 8oxoG lesions. T. cruzi cells overexpressing pol β are more resistant to ROS and are also more efficient to repair 8oxoG compared to control cells. Pol β seems to play a role in kDNA replication, since it associates with kinetoplast antipodal sites in those development stages in trypanosomatids which are competent for cell replication. ROS treatment of cells induces the overexpression of pol β, indicating that plays a role in kDNA repair. In this review, we will summarize the main features of trypanosomatid minicircle kDNA replication and the biochemical characteristics of pol β-like enzymes and their involvement in BER and kDNA replication. We also summarize key structural features of trypanosomatid pol β compared to their mammalian (human) counterpart. |
| first_indexed | 2024-12-13T20:01:09Z |
| format | Article |
| id | doaj.art-05abaac098c44951ba4aa6aa42e376d2 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T20:01:09Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-05abaac098c44951ba4aa6aa42e376d22022-12-21T23:33:11ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-08-011110.3389/fcimb.2021.670564670564Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From TrypanosomatidsEdio Maldonado0Sebastian Morales-Pison1Fabiola Urbina2Aldo Solari3Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileLaboratorio de Genética Molecular Humana, Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChilePrograma de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChilePrograma de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileTrypanosomatids are a group of primitive unicellular eukaryotes that can cause diseases in plants, insects, animals, and humans. Kinetoplast genome integrity is key to trypanosomatid cell survival and viability. Kinetoplast DNA (kDNA) is usually under attack by reactive oxygen and nitric species (ROS and RNS), damaging the DNA, and the cells must remove and repair those oxidatively generated lesions in order to survive and proliferate. Base excision repair (BER) is a well-conserved pathway for DNA repair after base damage, single-base loss, and single-strand breaks, which can arise from ROS, RSN, environmental genotoxic agents, and UV irradiation. A powerful BER system has been described in the T. cruzi kinetoplast and it is mainly carried out by DNA polymerase β (pol β) and DNA polymerase β-PAK (pol β-PAK), which are kinetoplast-located in T. cruzi as well as in other trypanosomatids. Both pol β and pol β-PAK belong to the X-family of DNA polymerases (pol X family), perform BER in trypanosomatids, and display intrinsic 5-deoxyribose phosphate (dRP) lyase and DNA polymerase activities. However, only Pol β-PAK is able to carry out trans-lesion synthesis (TLS) across 8oxoG lesions. T. cruzi cells overexpressing pol β are more resistant to ROS and are also more efficient to repair 8oxoG compared to control cells. Pol β seems to play a role in kDNA replication, since it associates with kinetoplast antipodal sites in those development stages in trypanosomatids which are competent for cell replication. ROS treatment of cells induces the overexpression of pol β, indicating that plays a role in kDNA repair. In this review, we will summarize the main features of trypanosomatid minicircle kDNA replication and the biochemical characteristics of pol β-like enzymes and their involvement in BER and kDNA replication. We also summarize key structural features of trypanosomatid pol β compared to their mammalian (human) counterpart.https://www.frontiersin.org/articles/10.3389/fcimb.2021.670564/fullTrypanosoma cruziDNA polymerase betakinetoplast DNAtrypanosomatidsBER |
| spellingShingle | Edio Maldonado Sebastian Morales-Pison Fabiola Urbina Aldo Solari Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids Frontiers in Cellular and Infection Microbiology Trypanosoma cruzi DNA polymerase beta kinetoplast DNA trypanosomatids BER |
| title | Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids |
| title_full | Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids |
| title_fullStr | Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids |
| title_full_unstemmed | Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids |
| title_short | Molecular and Functional Characteristics of DNA Polymerase Beta-Like Enzymes From Trypanosomatids |
| title_sort | molecular and functional characteristics of dna polymerase beta like enzymes from trypanosomatids |
| topic | Trypanosoma cruzi DNA polymerase beta kinetoplast DNA trypanosomatids BER |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.670564/full |
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