The proteolytic YB-1 fragment interacts with DNA repair machinery and enhances survival during DNA damaging stress |
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Authors: | Ekaterina R Kim Anastasia A Selyutina Ilya A Buldakov Valentina Evdokimova Lev P Ovchinnikov Alexey V Sorokin |
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Institution: | 1.Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation;2.University of Tartu; Institute of Technology; Tartu, Estonia;3.Department of Molecular Oncology; British Columbia Cancer Research Centre; Vancouver, British Columbia, Canada |
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Abstract: | The Y-box binding protein 1 (YB-1) is a DNA/RNA-binding nucleocytoplasmic shuttling protein whose regulatory effect on many DNA and RNA-dependent events is determined by its localization in the cell. We have shown previously that YB-1 is cleaved by 20S proteasome between E219 and G220, and the truncated N-terminal YB-1 fragment accumulates in the nuclei of cells treated with DNA damaging drugs. We proposed that appearance of truncated YB-1 in the nucleus may predict multiple drug resistance. Here, we compared functional activities of the full-length and truncated YB-1 proteins and showed that the truncated form was more efficient in protecting cells against doxorubicin treatment. Both forms of YB-1 induced changes in expression of various genes without affecting those responsible for drug resistance. Interestingly, although YB-1 cleavage did not significantly affect its DNA binding properties, truncated YB-1 was detected in complexes with Mre11 and Rad50 under genotoxic stress conditions. We conclude that both full-length and truncated YB-1 are capable of protecting cells against DNA damaging agents, and the truncated form may have an additional function in DNA repair. |
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Keywords: | drug resistance DNA damage proteasome YB-1 cleavage truncation DNA reparation PEST nuclear localization |
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