DNA damage regulation and its role in drug-related phenotypes in the malaria parasites
DNA of malaria parasites, Plasmodium falciparum, is subjected to extraordinary high levels of genotoxic insults during its complex life cycle within both the mosquito and human host. Accordingly, most of the components of DNA repair machinery are conserved in the parasite genome. Here, we investigat...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/80806 http://hdl.handle.net/10220/46602 |
| _version_ | 1811678006914056192 |
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| author | Gupta, Devendra Kumar Patra, Alok Tanala Zhu, Lei Gupta, Archana Patkar Bozdech, Zbynek |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Gupta, Devendra Kumar Patra, Alok Tanala Zhu, Lei Gupta, Archana Patkar Bozdech, Zbynek |
| author_sort | Gupta, Devendra Kumar |
| collection | NTU |
| description | DNA of malaria parasites, Plasmodium falciparum, is subjected to extraordinary high levels of genotoxic insults during its complex life cycle within both the mosquito and human host. Accordingly, most of the components of DNA repair machinery are conserved in the parasite genome. Here, we investigated the genome-wide responses of P. falciparum to DNA damaging agents and provided transcriptional evidence of the existence of the double strand break and excision repair system. We also showed that acetylation at H3K9, H4K8, and H3K56 play a role in the direct and indirect response to DNA damage induced by an alkylating agent, methyl methanesulphonate (MMS). Artemisinin, the first line antimalarial chemotherapeutics elicits a similar response compared to MMS which suggests its activity as a DNA damaging agent. Moreover, in contrast to the wild-type P. falciparum, two strains (Dd2 and W2) previously shown to exhibit a mutator phenotype, fail to induce their DNA repair upon MMS-induced DNA damage. Genome sequencing of the two mutator strains identified point mutations in 18 DNA repair genes which may contribute to this phenomenon. |
| first_indexed | 2024-10-01T02:46:24Z |
| format | Journal Article |
| id | ntu-10356/80806 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:46:24Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/808062023-02-28T16:59:51Z DNA damage regulation and its role in drug-related phenotypes in the malaria parasites Gupta, Devendra Kumar Patra, Alok Tanala Zhu, Lei Gupta, Archana Patkar Bozdech, Zbynek School of Biological Sciences DNA Repair DRNTU::Science::Biological sciences DNA Damage DNA of malaria parasites, Plasmodium falciparum, is subjected to extraordinary high levels of genotoxic insults during its complex life cycle within both the mosquito and human host. Accordingly, most of the components of DNA repair machinery are conserved in the parasite genome. Here, we investigated the genome-wide responses of P. falciparum to DNA damaging agents and provided transcriptional evidence of the existence of the double strand break and excision repair system. We also showed that acetylation at H3K9, H4K8, and H3K56 play a role in the direct and indirect response to DNA damage induced by an alkylating agent, methyl methanesulphonate (MMS). Artemisinin, the first line antimalarial chemotherapeutics elicits a similar response compared to MMS which suggests its activity as a DNA damaging agent. Moreover, in contrast to the wild-type P. falciparum, two strains (Dd2 and W2) previously shown to exhibit a mutator phenotype, fail to induce their DNA repair upon MMS-induced DNA damage. Genome sequencing of the two mutator strains identified point mutations in 18 DNA repair genes which may contribute to this phenomenon. Published version 2018-11-08T05:05:23Z 2019-12-06T13:59:21Z 2018-11-08T05:05:23Z 2019-12-06T13:59:21Z 2016 Journal Article Gupta, D. K., Patra, A. T., Zhu, L., Gupta, A. P., & Bozdech, Z. (2016). DNA damage regulation and its role in drug-related phenotypes in the malaria parasites. Scientific Reports, 6, 23603-. doi:10.1038/srep23603 https://hdl.handle.net/10356/80806 http://hdl.handle.net/10220/46602 10.1038/srep23603 27033103 en Scientific Reports © 2016 The Authors (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 15 p. application/pdf |
| spellingShingle | DNA Repair DRNTU::Science::Biological sciences DNA Damage Gupta, Devendra Kumar Patra, Alok Tanala Zhu, Lei Gupta, Archana Patkar Bozdech, Zbynek DNA damage regulation and its role in drug-related phenotypes in the malaria parasites |
| title | DNA damage regulation and its role in drug-related phenotypes in the malaria parasites |
| title_full | DNA damage regulation and its role in drug-related phenotypes in the malaria parasites |
| title_fullStr | DNA damage regulation and its role in drug-related phenotypes in the malaria parasites |
| title_full_unstemmed | DNA damage regulation and its role in drug-related phenotypes in the malaria parasites |
| title_short | DNA damage regulation and its role in drug-related phenotypes in the malaria parasites |
| title_sort | dna damage regulation and its role in drug related phenotypes in the malaria parasites |
| topic | DNA Repair DRNTU::Science::Biological sciences DNA Damage |
| url | https://hdl.handle.net/10356/80806 http://hdl.handle.net/10220/46602 |
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