The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway.
Protein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the Fanconi anemia (FA) protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are requir...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1797100660303331328 |
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| author | Nijman, S Huang, T Dirac, A Brummelkamp, T Kerkhoven, R D'Andrea, A Bernards, R |
| author_facet | Nijman, S Huang, T Dirac, A Brummelkamp, T Kerkhoven, R D'Andrea, A Bernards, R |
| author_sort | Nijman, S |
| collection | OXFORD |
| description | Protein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the Fanconi anemia (FA) protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are required for FANCD2 ubiquitination. By screening a gene family RNAi library, we identify the deubiquitinating enzyme USP1 as a novel component of the Fanconi anemia pathway. Inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2. Furthermore, USP1 physically associates with FANCD2, and the proteins colocalize in chromatin after DNA damage. Finally, analysis of crosslinker-induced chromosomal aberrations in USP1 knockdown cells suggests a role in DNA repair. We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2. |
| first_indexed | 2024-03-07T05:40:44Z |
| format | Journal article |
| id | oxford-uuid:e57a4ee4-1eac-44e5-8ebf-d32cf9937c4a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:40:44Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:e57a4ee4-1eac-44e5-8ebf-d32cf9937c4a2022-03-27T10:24:13ZThe deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e57a4ee4-1eac-44e5-8ebf-d32cf9937c4aEnglishSymplectic Elements at Oxford2005Nijman, SHuang, TDirac, ABrummelkamp, TKerkhoven, RD'Andrea, ABernards, RProtein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the Fanconi anemia (FA) protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are required for FANCD2 ubiquitination. By screening a gene family RNAi library, we identify the deubiquitinating enzyme USP1 as a novel component of the Fanconi anemia pathway. Inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2. Furthermore, USP1 physically associates with FANCD2, and the proteins colocalize in chromatin after DNA damage. Finally, analysis of crosslinker-induced chromosomal aberrations in USP1 knockdown cells suggests a role in DNA repair. We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2. |
| spellingShingle | Nijman, S Huang, T Dirac, A Brummelkamp, T Kerkhoven, R D'Andrea, A Bernards, R The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. |
| title | The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. |
| title_full | The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. |
| title_fullStr | The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. |
| title_full_unstemmed | The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. |
| title_short | The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. |
| title_sort | deubiquitinating enzyme usp1 regulates the fanconi anemia pathway |
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