| Autor: |
Patrick M. Lombardi, Nima Mosammaparast, Emmanuella Osei-Asante, Dhane P. Schmelyun, Timur Rusanov, Lauren N. Gray, Rebecca Rodell, Julia G. Baer, Kayla R. Kebreau, Rita Anoh, Shaheer H. Syed, Kate A. Burke, Devin E. Shorb, Abigail R. Hacker, Ananya Majumdar, Christine K. Ngandu, Hannah A. Orland, Sara Haile, Cynthia Wolberger, Julianna M. Veilleux |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Alkylation of DNA and RNA is a potentially toxic lesion that can result in mutations and cell death. In response to alkylation damage, K63-linked polyubiquitin chains are assembled that localize the ALKBH3-ASCC repair complex to damage sites in the nucleus. The protein ASCC2, a subunit of the ASCC complex, selectively binds K63-linked polyubiquitin chains using its CUE domain, a type of ubiquitin-binding domain that typically binds monoubiquitin and does not discriminate among different polyubiquitin linkage types. We report here that the ASCC2 CUE domain selectively binds K63-linked diubiquitin by contacting both the distal and proximal ubiquitin. Whereas the ASCC2 CUE domain binds the distal ubiquitin in a manner similar to that reported for other CUE domains bound to a single ubiquitin, the contacts with the proximal ubiquitin are unique to ASCC2. The N-terminal portion of the ASCC2 α1 helix, including residues E467 and S470, contributes to the binding interaction with the proximal ubiquitin of K63-linked diubiquitin. Mutation of residues within the N-terminal portion of the ASCC2 α1 helix decreases ASCC2 recruitment in response to DNA alkylation, supporting the functional significance of these interactions during the alkylation damage response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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