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USP45 deubiquitinates ERCC1. 12 / 12
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"It was shown that USP45 interacts with and deubiquitinates the excision repair cross complementation group 1 (ERCC1) subunit of the XPF-ERCC1 DNA repair nuclease which has role in the TC-NER of UV induced DNA damage [XREF_BIBR, XREF_BIBR]."
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"As expected, the catalytically inactive USP45 [Cys199Ala] mutant also failed to deubiquitylate ERCC1 (Fig XREF_FIG C, XREF_SUPPLEMENTARY)."
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"Upon UV exposure, USP45 interacts with ERCC1-XPF but the USP45 mutant (Asp25Ala, Glu26Ala) that is catalytically active but that can not bind to ERCC1 failed to deubiquitinate ERCC1."
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"USP45 targeting ERCC1"
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"This, coupled with the report that inactivating the USP45 protein that deubiquitinates ERCC1 in human myelogenous leukaemia and osteosarcoma cells leads to reduced levels of NER and increased sensitivity to UV irradiation [XREF_BIBR], suggests that our therapeutic strategy is likely applicable to a wide range of human cancers."
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"Furthermore, USP45 can deubiquitylate ERCC1 in a manner that requires association of USP45 and ERCC1."
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"These data therefore indicate that likely the ubiquitylation of ERCC1, which is reversed by USP45, controls an aspect of ERCC1 function other than regulating its stability."
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"In this light, we observed that 5 other DUBs tested (AMSH, Cezanne, OTUB1, UCHL1 and USP27X) failed to deubiquitylate ERCC1 under conditions that wild-type USP45 deubiquitylated ERCC1 (Supplementary Fig S5C)."
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"The major role of ERCC1 deubiquitination by USP45 has been speculated to enable ERCC1-XPF to gain access to DNA damage sites."
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"Both mass spectrometry and yeast two-hybrid system identify that USP45 interacts with ERCC1, and it was also demonstrated that USP45 deubiquitinates ERCC1 [55]."
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"ERCC1 can be deubiquitinated by USP45, which promotes XPF-ERCC1 recruitment to sites of DNA damage [XREF_BIBR]."
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"Thus, the major role of ERCC1 deubiquitylation by USP45 may be to enable ERCC1-XPF to gain access to DNA damage sites."
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