The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death
The proper maintenance of genetic material is essential for the survival of living organisms. One of the main safeguards of genome stability is homologous recombination involved in the faithful repair of DNA double-strand breaks, the restoration of collapsed replication forks, and the bypass of repl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/5/1450 |
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| author | Tadas Andriuskevicius Anton Dubenko Svetlana Makovets |
| author_facet | Tadas Andriuskevicius Anton Dubenko Svetlana Makovets |
| author_sort | Tadas Andriuskevicius |
| collection | DOAJ |
| description | The proper maintenance of genetic material is essential for the survival of living organisms. One of the main safeguards of genome stability is homologous recombination involved in the faithful repair of DNA double-strand breaks, the restoration of collapsed replication forks, and the bypass of replication barriers. Homologous recombination relies on the formation of Rad51 nucleoprotein filaments which are responsible for the homology-based interactions between DNA strands. Here, we demonstrate that without the regulation of these filaments by Srs2 and Rad54, which are known to remove Rad51 from single-stranded and double-stranded DNA, respectively, the filaments strongly inhibit damage-associated DNA synthesis during DNA repair. Furthermore, this regulation is essential for cell survival under normal growth conditions, as in the <i>srs2Δ rad54Δ</i> mutants, unregulated Rad51 nucleoprotein filaments cause activation of the DNA damage checkpoint, formation of mitotic bridges, and loss of genetic material. These genome instability features may stem from the problems at stalled replication forks as the lack of Srs2 and Rad54 in the presence of Rad51 nucleoprotein filaments impedes cell recovery from replication stress. This study demonstrates that the timely and efficient disassembly of recombination machinery is essential for genome maintenance and cell survival. |
| first_indexed | 2024-03-11T03:55:05Z |
| format | Article |
| id | doaj.art-c1a65d2435924993a15b308af2c7dad1 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:55:05Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-c1a65d2435924993a15b308af2c7dad12023-11-18T00:37:17ZengMDPI AGBiomedicines2227-90592023-05-01115145010.3390/biomedicines11051450The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell DeathTadas Andriuskevicius0Anton Dubenko1Svetlana Makovets2Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Alexander Crum Brown Road, Edinburgh EH9 3FF, UKInstitute of Cell Biology, School of Biological Sciences, University of Edinburgh, Alexander Crum Brown Road, Edinburgh EH9 3FF, UKInstitute of Cell Biology, School of Biological Sciences, University of Edinburgh, Alexander Crum Brown Road, Edinburgh EH9 3FF, UKThe proper maintenance of genetic material is essential for the survival of living organisms. One of the main safeguards of genome stability is homologous recombination involved in the faithful repair of DNA double-strand breaks, the restoration of collapsed replication forks, and the bypass of replication barriers. Homologous recombination relies on the formation of Rad51 nucleoprotein filaments which are responsible for the homology-based interactions between DNA strands. Here, we demonstrate that without the regulation of these filaments by Srs2 and Rad54, which are known to remove Rad51 from single-stranded and double-stranded DNA, respectively, the filaments strongly inhibit damage-associated DNA synthesis during DNA repair. Furthermore, this regulation is essential for cell survival under normal growth conditions, as in the <i>srs2Δ rad54Δ</i> mutants, unregulated Rad51 nucleoprotein filaments cause activation of the DNA damage checkpoint, formation of mitotic bridges, and loss of genetic material. These genome instability features may stem from the problems at stalled replication forks as the lack of Srs2 and Rad54 in the presence of Rad51 nucleoprotein filaments impedes cell recovery from replication stress. This study demonstrates that the timely and efficient disassembly of recombination machinery is essential for genome maintenance and cell survival.https://www.mdpi.com/2227-9059/11/5/1450budding yeastRad51 nucleoprotein filament disassemblyRad54 and Srs2stalled replication forksmitotic bridges |
| spellingShingle | Tadas Andriuskevicius Anton Dubenko Svetlana Makovets The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death Biomedicines budding yeast Rad51 nucleoprotein filament disassembly Rad54 and Srs2 stalled replication forks mitotic bridges |
| title | The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death |
| title_full | The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death |
| title_fullStr | The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death |
| title_full_unstemmed | The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death |
| title_short | The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death |
| title_sort | inability to disassemble rad51 nucleoprotein filaments leads to aberrant mitosis and cell death |
| topic | budding yeast Rad51 nucleoprotein filament disassembly Rad54 and Srs2 stalled replication forks mitotic bridges |
| url | https://www.mdpi.com/2227-9059/11/5/1450 |
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