Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast.
Nucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found the D...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826302481309630464 |
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| author | Moss, J Tinline-Purvis, H Walker, C Folkes, L Stratford, MR Hayles, J Hoe, K Kim, D Park, H Kearsey, S Fleck, O Holmberg, C Nielsen, O Humphrey, T |
| author_facet | Moss, J Tinline-Purvis, H Walker, C Folkes, L Stratford, MR Hayles, J Hoe, K Kim, D Park, H Kearsey, S Fleck, O Holmberg, C Nielsen, O Humphrey, T |
| author_sort | Moss, J |
| collection | OXFORD |
| description | Nucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found the Ddb1-Cul4(Cdt)² ubiquitin ligase complex and ribonucleotide reductase (RNR) to be required for HR repair of a DNA double-strand break (DSB). The Ddb1-Cul4(Cdt)² ubiquitin ligase complex is required for degradation of Spd1, an inhibitor of RNR in fission yeast. Accordingly, deleting spd1(+) suppressed the DNA damage sensitivity and the reduced HR efficiency associated with loss of ddb1(+) or cdt2(+). Furthermore, we demonstrate a role for nucleotide synthesis in postsynaptic gap filling of resected ssDNA ends during HR repair. Finally, we define a role for Rad3 (ATR) in nucleotide synthesis and HR through increasing Cdt2 nuclear levels in response to DNA damage. Our findings support a model in which break-induced Rad3 and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent Spd1 degradation and RNR activation promotes postsynaptic ssDNA gap filling during HR repair. |
| first_indexed | 2024-03-07T05:48:11Z |
| format | Journal article |
| id | oxford-uuid:e7ee4290-f1fd-46c1-9ee1-c7ba2899f0d1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:48:11Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:e7ee4290-f1fd-46c1-9ee1-c7ba2899f0d12022-03-27T10:42:49ZBreak-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e7ee4290-f1fd-46c1-9ee1-c7ba2899f0d1EnglishSymplectic Elements at Oxford2010Moss, JTinline-Purvis, HWalker, CFolkes, LStratford, MRHayles, JHoe, KKim, DPark, HKearsey, SFleck, OHolmberg, CNielsen, OHumphrey, TNucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found the Ddb1-Cul4(Cdt)² ubiquitin ligase complex and ribonucleotide reductase (RNR) to be required for HR repair of a DNA double-strand break (DSB). The Ddb1-Cul4(Cdt)² ubiquitin ligase complex is required for degradation of Spd1, an inhibitor of RNR in fission yeast. Accordingly, deleting spd1(+) suppressed the DNA damage sensitivity and the reduced HR efficiency associated with loss of ddb1(+) or cdt2(+). Furthermore, we demonstrate a role for nucleotide synthesis in postsynaptic gap filling of resected ssDNA ends during HR repair. Finally, we define a role for Rad3 (ATR) in nucleotide synthesis and HR through increasing Cdt2 nuclear levels in response to DNA damage. Our findings support a model in which break-induced Rad3 and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent Spd1 degradation and RNR activation promotes postsynaptic ssDNA gap filling during HR repair. |
| spellingShingle | Moss, J Tinline-Purvis, H Walker, C Folkes, L Stratford, MR Hayles, J Hoe, K Kim, D Park, H Kearsey, S Fleck, O Holmberg, C Nielsen, O Humphrey, T Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. |
| title | Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. |
| title_full | Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. |
| title_fullStr | Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. |
| title_full_unstemmed | Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. |
| title_short | Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. |
| title_sort | break induced atr and ddb1 cul4 cdt ² ubiquitin ligase dependent nucleotide synthesis promotes homologous recombination repair in fission yeast |
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