IndraLab

Statements

CDC45 binds USP37. 6 / 6
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"The second highest pair is USP37-CDC45, which is consistent with our previous finding that USP37 interacts with CMG complexes xref ."
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"Moreover, AlphaFold made strong reciprocal predictions that USP37 and CDC45 interact, highlighting CDC45 as a likely tethering point for USP37 at the replisome."
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"Furthermore, consistent with the USP37-CDC45 interaction having an important function, the predicted binding surface of USP37, as well as the interacting residues, are highly conserved between human and Xenopus ( xref – xref )."
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"To test the function of the predicted USP37-CDC45 interaction, we mutated eight highly conserved USP37 residues at the predicted interface to alanine, generating USP37 8A ( xref )."
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"Finally, to monitor whether the USP37-CDC45 interaction is important, we monitored the sensitivity to genotoxic agents of USP37 KO cells complemented with an empty vector (E.V), USP37 WT , or USP37 8A ."
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"Collectively, these data suggested that USP37’s interaction with CDC45 counteracts TRAIP-mediated CMG ubiquitylation, which mitigates the toxic effects of topoisomerase inhibitors."
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