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首页> 外文期刊>EMBO Journal >Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway
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Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway

机译：Ubiquitin-like UBL5促进蛋白质功能的完整性Fanconi贫血通路

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摘要

Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway.
机译：泛素和ubiquitin-like蛋白质(ubl)函数在一个广泛的细胞过程。UBL5是一个非典型UBL不形式共价与细胞蛋白质和配合在调制pre-mRNA已知作用拼接。人类UBL5参与推动Fanconi贫血(FA)通路的功能修复的DNA交联interstrand(民),由一个特定的交互中央FANCI FA途径组件。UBL5-deficient细胞显示spliceosome-independent减少FANCI蛋白质稳定性、FANCI功能缺陷响应DNA损伤和过敏症民。底层UBL5-FANCI绑定,我们生成的separation-of-function突变体来演示FA途径的关键方面功能,包括FANCI-FANCD2 heterodimerization FANCD2和FANCI monoubiquitylation和维护民后,染色体稳定性大打折扣当UBL5-FANCI交互是选择性的抑制突变的蛋白质。在一起,我们的研究结果建立UBL5作为一个因素促进足总DNA的功能修复途径。

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