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Cell Cycle. 2013 Dec 15;12(24):3791-803. doi: 10.4161/cc.26670. Epub 2013 Oct 7.

The proteolytic YB-1 fragment interacts with DNA repair machinery and enhances survival during DNA damaging stress.

Author information

1
Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation.
2
Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation; University of Tartu; Institute of Technology; Tartu, Estonia.
3
Institute of Protein Research; Russian Academy of Sciences; Pushchino, Moscow Region, Russian Federation; Department of Molecular Oncology; British Columbia Cancer Research Centre; Vancouver, British Columbia, Canada.

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.

KEYWORDS:

DNA damage; DNA reparation; PEST; YB-1; cleavage; drug resistance; nuclear localization; proteasome; truncation

PMID:
24107631
PMCID:
PMC3905071
DOI:
10.4161/cc.26670
[Indexed for MEDLINE]
Free PMC Article

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