WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair
The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs). Many FA proteins are recruited to ICLs in a timely fashion so that coordinated repair can occur. However, the mechanism of this process is poorly understood. Here, we report the purification of a FANCD2-containing protein com...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2020
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| _version_ | 1826285349516607488 |
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| author | Socha, A Yang, D Bulsiewicz, A Yaprianto, K Kupculak, M Liang, C-C Hadjicharalambous, A Wu, R Gygi, SP Cohn, MA |
| author_facet | Socha, A Yang, D Bulsiewicz, A Yaprianto, K Kupculak, M Liang, C-C Hadjicharalambous, A Wu, R Gygi, SP Cohn, MA |
| author_sort | Socha, A |
| collection | OXFORD |
| description | The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs). Many FA proteins are recruited to ICLs in a timely fashion so that coordinated repair can occur. However, the mechanism of this process is poorly understood. Here, we report the purification of a FANCD2-containing protein complex with multiple subunits, including WRNIP1. Using live-cell imaging, we show that WRNIP1 is recruited to ICLs quickly after their appearance, promoting repair. The observed recruitment facilitates subsequent recruitment of the FANCD2/FANCI complex. Depletion of WRNIP1 sensitizes cells to ICL-forming drugs. We find that ubiquitination of WRNIP1 and the activity of its UBZ domain are required to facilitate recruitment of FANCD2/FANCI and promote repair. Altogether, we describe a mechanism by which WRNIP1 is recruited rapidly to ICLs, resulting in chromatin loading of the FANCD2/FANCI complex in an unusual process entailing ubiquitination of WRNIP1 and the activity of its integral UBZ domain. |
| first_indexed | 2024-03-07T01:27:30Z |
| format | Journal article |
| id | oxford-uuid:927717c3-d482-4141-a156-7db0602ba526 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:27:30Z |
| publishDate | 2020 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:927717c3-d482-4141-a156-7db0602ba5262022-03-26T23:25:45ZWRNIP1 is recruited to DNA interstrand crosslinks and promotes repairJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:927717c3-d482-4141-a156-7db0602ba526EnglishSymplectic ElementsElsevier2020Socha, AYang, DBulsiewicz, AYaprianto, KKupculak, MLiang, C-CHadjicharalambous, AWu, RGygi, SPCohn, MAThe Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs). Many FA proteins are recruited to ICLs in a timely fashion so that coordinated repair can occur. However, the mechanism of this process is poorly understood. Here, we report the purification of a FANCD2-containing protein complex with multiple subunits, including WRNIP1. Using live-cell imaging, we show that WRNIP1 is recruited to ICLs quickly after their appearance, promoting repair. The observed recruitment facilitates subsequent recruitment of the FANCD2/FANCI complex. Depletion of WRNIP1 sensitizes cells to ICL-forming drugs. We find that ubiquitination of WRNIP1 and the activity of its UBZ domain are required to facilitate recruitment of FANCD2/FANCI and promote repair. Altogether, we describe a mechanism by which WRNIP1 is recruited rapidly to ICLs, resulting in chromatin loading of the FANCD2/FANCI complex in an unusual process entailing ubiquitination of WRNIP1 and the activity of its integral UBZ domain. |
| spellingShingle | Socha, A Yang, D Bulsiewicz, A Yaprianto, K Kupculak, M Liang, C-C Hadjicharalambous, A Wu, R Gygi, SP Cohn, MA WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair |
| title | WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair |
| title_full | WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair |
| title_fullStr | WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair |
| title_full_unstemmed | WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair |
| title_short | WRNIP1 is recruited to DNA interstrand crosslinks and promotes repair |
| title_sort | wrnip1 is recruited to dna interstrand crosslinks and promotes repair |
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