Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.
Replication protein A (RPA) is a heterotrimeric complex and the major single-strand DNA (ssDNA) binding protein in eukaryotes. It plays important roles in DNA replication, repair, recombination, telomere maintenance, and checkpoint signaling. Because RPA is essential for cell survival, understanding...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010691 |
| _version_ | 1797377805102612480 |
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| author | Yong-Jie Xu Sankhadip Bhadra Alaa Taha A Mahdi Kamal Dev Ilknur Yurtsever Toru M Nakamura |
| author_facet | Yong-Jie Xu Sankhadip Bhadra Alaa Taha A Mahdi Kamal Dev Ilknur Yurtsever Toru M Nakamura |
| author_sort | Yong-Jie Xu |
| collection | DOAJ |
| description | Replication protein A (RPA) is a heterotrimeric complex and the major single-strand DNA (ssDNA) binding protein in eukaryotes. It plays important roles in DNA replication, repair, recombination, telomere maintenance, and checkpoint signaling. Because RPA is essential for cell survival, understanding its checkpoint signaling function in cells has been challenging. Several RPA mutants have been reported previously in fission yeast. None of them, however, has a defined checkpoint defect. A separation-of-function mutant of RPA, if identified, would provide significant insights into the checkpoint initiation mechanisms. We have explored this possibility and carried out an extensive genetic screen for Rpa1/Ssb1, the large subunit of RPA in fission yeast, looking for mutants with defects in checkpoint signaling. This screen has identified twenty-five primary mutants that are sensitive to genotoxins. Among these mutants, two have been confirmed partially defective in checkpoint signaling primarily at the replication fork, not the DNA damage site. The remaining mutants are likely defective in other functions such as DNA repair or telomere maintenance. Our screened mutants, therefore, provide a valuable tool for future dissection of the multiple functions of RPA in fission yeast. |
| first_indexed | 2024-03-08T19:57:42Z |
| format | Article |
| id | doaj.art-f820d48660ac4b31823c8bd998e4ca66 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-03-08T19:57:42Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-f820d48660ac4b31823c8bd998e4ca662023-12-24T05:32:40ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-05-01195e101069110.1371/journal.pgen.1010691Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.Yong-Jie XuSankhadip BhadraAlaa Taha A MahdiKamal DevIlknur YurtseverToru M NakamuraReplication protein A (RPA) is a heterotrimeric complex and the major single-strand DNA (ssDNA) binding protein in eukaryotes. It plays important roles in DNA replication, repair, recombination, telomere maintenance, and checkpoint signaling. Because RPA is essential for cell survival, understanding its checkpoint signaling function in cells has been challenging. Several RPA mutants have been reported previously in fission yeast. None of them, however, has a defined checkpoint defect. A separation-of-function mutant of RPA, if identified, would provide significant insights into the checkpoint initiation mechanisms. We have explored this possibility and carried out an extensive genetic screen for Rpa1/Ssb1, the large subunit of RPA in fission yeast, looking for mutants with defects in checkpoint signaling. This screen has identified twenty-five primary mutants that are sensitive to genotoxins. Among these mutants, two have been confirmed partially defective in checkpoint signaling primarily at the replication fork, not the DNA damage site. The remaining mutants are likely defective in other functions such as DNA repair or telomere maintenance. Our screened mutants, therefore, provide a valuable tool for future dissection of the multiple functions of RPA in fission yeast.https://doi.org/10.1371/journal.pgen.1010691 |
| spellingShingle | Yong-Jie Xu Sankhadip Bhadra Alaa Taha A Mahdi Kamal Dev Ilknur Yurtsever Toru M Nakamura Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. PLoS Genetics |
| title | Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. |
| title_full | Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. |
| title_fullStr | Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. |
| title_full_unstemmed | Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. |
| title_short | Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. |
| title_sort | comprehensive mutational analysis of the checkpoint signaling function of rpa1 ssb1 in fission yeast |
| url | https://doi.org/10.1371/journal.pgen.1010691 |
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