Qing P, Han L, Bin L, Yan L, Ping WX

Human helicase-like transcription factor (HLTF) is a functional homologue of yeast Rad5 that regulates error-free replication through DNA lesions. HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability. Here, we identified the deubiquitylating enzyme ubiquitin-specific protease 7 (USP7) as a novel ...

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regulator of HLTF stability. We found that USP7 interacted with and stabilized HLTF after genotoxic stress. Furthermore, USP7 mediated deubiquitination significantly prolonged the half-life of HLTF, which in turn increased PCNA polyubiquitination. More intriguingly, Silencing of USP7 rendered A549 cells highly sensitive to DNA damage and over-expression of HLTF attenuated this sensitivity. Thus, our results delineate a previously unknown USP7-HLTF-PCNA molecular network controlling DNA damage response. J. Cell. Biochem. © 2011 Wiley-Liss, Inc.

Date: Aug. 15, 2011

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