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The histone and non-histone methyllysine reader activities of the UHRF1 tandem Tudor domain are dispensable for the propagation of aberrant DNA methylation patterning in cancer cells by Vaughan, Robert M.; Kupai, Ariana; Foley, Caroline A.; Sagum, Cari A.; Tibben, Bailey M.; Eden, Hope E.; Tiedemann, Rochelle L.; Berryhill, Christine A.; Patel, Varun; Shaw, Kevin M.; Krajewski, Krzysztof; Strahl, Brian D.; Bedford, Mark T.; Frye, Stephen V.; Dickson, Bradley M.; Rothbart, Scott B. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract The chromatin-binding E3 ubiquitin ligase ubiquitin-like with PHD and RING finger domains 1 (UHRF1) contributes to the maintenance of aberrant DNA methylation patterning in cancer cells through multivalent histone and DNA recognition. The tandem Tudor domain (TTD) of UHRF1 is well-characterized as a reader of lysine 9 di- and tri-methylation on histone H3 (H3K9me2/me3) and, more recently, lysine 126 di- and tri-methylation on DNA ligase 1 (LIG1K126me2/me3). However, the functional significance and selectivity of these interactions remain unclear. In this study, we used protein domain microarrays to search for additional readers of LIG1K126me2, the preferred methyl state bound by the UHRF1 TTD. We show that the UHRF1 TTD binds LIG1K126me2 with high affinity and selectivity compared to other known methyllysine readers. Notably, and unlike H3K9me2/me3, the UHRF1 plant homeodomain (PHD) and its N-terminal linker (L2) do not contribute to multivalent LIG1K126me2 recognition along with the TTD. To test the functional significance of this interaction, we designed a LIG1K126me2 cell-penetrating peptide (CPP). Consistent with LIG1 knockdown, uptake of the CPP had no significant

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Author
Vaughan, Robert M.; Kupai, Ariana; Foley, Caroline A.; Sagum, Cari A.; Tibben, Bailey M.; Eden, Hope E.; Tiedemann, Rochelle L.; Berryhill, Christine A.; Patel, Varun; Shaw, Kevin M.; Krajewski, Krzysztof; Strahl, Brian D.; Bedford, Mark T.; Frye, Stephen V.; Dickson, Bradley M.; Rothbart, Scott B.
Publisher
BioMed Central; Springer (Biomed Central Ltd.); [London]: BioMed Central; Springer Science and Business Media LLC (ISSN 1756-8935)
Published
2020
Language
EN
Field
Biochemistry, Genetics and Molecular Biology (Life Sciences)

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