Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents
Rts1 is a regulatory subunit of the trimeric protein phosphatase 2A phosphatase and it participates in many biological processes by modulating the phosphorylation status of proteins. Consistent with its role, mutants lacking Rts1 display multiple phenotypes. We have previously performed a high throu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.01117/full |
| _version_ | 1818291210657202176 |
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| author | Mustapha Aouida Abdelmoez Eshrif Dindial Ramotar Dindial Ramotar |
| author_facet | Mustapha Aouida Abdelmoez Eshrif Dindial Ramotar Dindial Ramotar |
| author_sort | Mustapha Aouida |
| collection | DOAJ |
| description | Rts1 is a regulatory subunit of the trimeric protein phosphatase 2A phosphatase and it participates in many biological processes by modulating the phosphorylation status of proteins. Consistent with its role, mutants lacking Rts1 display multiple phenotypes. We have previously performed a high throughput screen to search for yeast haploid mutants with altered sensitivity to the anticancer drug bleomycin, which acts by damaging the DNA to produce single and double strand breaks. RTS1 was among the genes that when singly deleted cause sensitivity to bleomycin. We investigate whether Rts1 plays a role in the repair of bleomycin-induced DNA lesions. We show that deletion of the RTS1 gene in the rad51 null background, lacking Rad51 known to be involved in the repair of bleomycin-induced DNA lesions, resulted in double mutants that were sensitized to bleomycin and not to other DNA damaging agents that creates DNA adducts. We further show that Rts1 has the ability to bind to DNA and in its absence cells displayed an increase in the frequency of both spontaneous and bleomycin-induced mutations compared to the parent. This is the first report implicating Rts1 with a role in DNA damage and repair, perhaps regulating the phosphorylation status of one or more proteins involved in the repair of DNA strand breaks. |
| first_indexed | 2024-12-13T02:40:27Z |
| format | Article |
| id | doaj.art-61cd549f6a8441b7a29afb8e73b52fc2 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-13T02:40:27Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-61cd549f6a8441b7a29afb8e73b52fc22022-12-22T00:02:19ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-11-011010.3389/fgene.2019.01117482590Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging AgentsMustapha Aouida0Abdelmoez Eshrif1Dindial Ramotar2Dindial Ramotar3College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha, QatarMaisonneuve-Rosemont Hospital, Research Center, Department of Medicine, Université de Montréal, Montréal, QC, CanadaCollege of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha, QatarMaisonneuve-Rosemont Hospital, Research Center, Department of Medicine, Université de Montréal, Montréal, QC, CanadaRts1 is a regulatory subunit of the trimeric protein phosphatase 2A phosphatase and it participates in many biological processes by modulating the phosphorylation status of proteins. Consistent with its role, mutants lacking Rts1 display multiple phenotypes. We have previously performed a high throughput screen to search for yeast haploid mutants with altered sensitivity to the anticancer drug bleomycin, which acts by damaging the DNA to produce single and double strand breaks. RTS1 was among the genes that when singly deleted cause sensitivity to bleomycin. We investigate whether Rts1 plays a role in the repair of bleomycin-induced DNA lesions. We show that deletion of the RTS1 gene in the rad51 null background, lacking Rad51 known to be involved in the repair of bleomycin-induced DNA lesions, resulted in double mutants that were sensitized to bleomycin and not to other DNA damaging agents that creates DNA adducts. We further show that Rts1 has the ability to bind to DNA and in its absence cells displayed an increase in the frequency of both spontaneous and bleomycin-induced mutations compared to the parent. This is the first report implicating Rts1 with a role in DNA damage and repair, perhaps regulating the phosphorylation status of one or more proteins involved in the repair of DNA strand breaks.https://www.frontiersin.org/article/10.3389/fgene.2019.01117/fullanticancer drug bleomycinmutagenesisphosphatase subunitDNA damageyeast |
| spellingShingle | Mustapha Aouida Abdelmoez Eshrif Dindial Ramotar Dindial Ramotar Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents Frontiers in Genetics anticancer drug bleomycin mutagenesis phosphatase subunit DNA damage yeast |
| title | Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents |
| title_full | Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents |
| title_fullStr | Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents |
| title_full_unstemmed | Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents |
| title_short | Yeast Lacking the PP2A Phosphatase Regulatory Subunit Rts1 Sensitizes rad51 Mutants to Specific DNA Damaging Agents |
| title_sort | yeast lacking the pp2a phosphatase regulatory subunit rts1 sensitizes rad51 mutants to specific dna damaging agents |
| topic | anticancer drug bleomycin mutagenesis phosphatase subunit DNA damage yeast |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.01117/full |
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