دورية أكاديمية
SPRTN patient variants cause global-genome DNA-protein crosslink repair defects
العنوان: | SPRTN patient variants cause global-genome DNA-protein crosslink repair defects |
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المؤلفون: | Pedro Weickert, Hao-Yi Li, Maximilian J. Götz, Sophie Dürauer, Denitsa Yaneva, Shubo Zhao, Jacqueline Cordes, Aleida C. Acampora, Ignasi Forne, Axel Imhof, Julian Stingele |
المصدر: | Nature Communications, Vol 14, Iss 1, Pp 1-14 (2023) |
بيانات النشر: | Nature Portfolio, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Science |
مصطلحات موضوعية: | Science |
الوصف: | Abstract DNA-protein crosslinks (DPCs) are pervasive DNA lesions that are induced by reactive metabolites and various chemotherapeutic agents. Here, we develop a technique for the Purification of x-linked Proteins (PxP), which allows identification and tracking of diverse DPCs in mammalian cells. Using PxP, we investigate DPC repair in cells genetically-engineered to express variants of the SPRTN protease that cause premature ageing and early-onset liver cancer in Ruijs-Aalfs syndrome patients. We find an unexpected role for SPRTN in global-genome DPC repair, that does not rely on replication-coupled detection of the lesion. Mechanistically, we demonstrate that replication-independent DPC cleavage by SPRTN requires SUMO-targeted ubiquitylation of the protein adduct and occurs in addition to proteasomal DPC degradation. Defective ubiquitin binding of SPRTN patient variants compromises global-genome DPC repair and causes synthetic lethality in combination with a reduction in proteasomal DPC repair capacity. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2041-1723 |
Relation: | https://doaj.org/toc/2041-1723 |
DOI: | 10.1038/s41467-023-35988-1 |
URL الوصول: | https://doaj.org/article/dc7e3a77ff704d98b30b8ecc3d84505f |
رقم الأكسشن: | edsdoj.7e3a77ff704d98b30b8ecc3d84505f |
قاعدة البيانات: | Directory of Open Access Journals |
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