IndraLab

Statements


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sparser
"The second highest pair is USP37-CDC45, which is consistent with our previous finding that USP37 interacts with CMG complexes xref ."

sparser
"Moreover, AlphaFold made strong reciprocal predictions that USP37 and CDC45 interact, highlighting CDC45 as a likely tethering point for USP37 at the replisome."

sparser
"Moreover, AlphaFold made strong reciprocal predictions that USP37 and CDC45 interact, highlighting CDC45 as a likely tethering point for USP37 at the replisome."

sparser
"Interestingly, association of USP37 WT but not USP37 8A with replicating DNA increased in cells treated with camptothecin, suggesting USP37’s interaction with CDC45 may increase in the presence of stress to preserve stressed replisomes."

sparser
"To test the function of the predicted USP37-CDC45 interaction, we made mutations in four highly conserved USP37 residues in the predicted left (R11A, N13A, K21A, and W22A) or right interfaces (K63A, R71A, D85A, and K86A), or in all eight residues, generating USP37 4A-L , USP37 4A-R , and USP37 8A , respectively (Supplementary Fig. xref )."

sparser
"Collectively, the data suggested that USP37’s interaction with CDC45 counteracts TRAIP-mediated CMG ubiquitylation, which mitigates the toxic effects of topoisomerase inhibitors."

sparser
"Furthermore, consistent with the USP37-CDC45 interaction having an important function, the predicted interacting residues within the left and right binding interfaces of USP37 are highly conserved between human and Xenopus (Supplementary Fig. xref )."

sparser
"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 )."

sparser
"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 )."

sparser
"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 ."

sparser
"Collectively, these data suggested that USP37’s interaction with CDC45 counteracts TRAIP-mediated CMG ubiquitylation, which mitigates the toxic effects of topoisomerase inhibitors."