Saridakis, Vivian2015-08-282015-08-282014-04-252015-08-28http://hdl.handle.net/10315/29858USP7 is a deubiquitinase implicated in processes such as DNA damage and tumor suppression. The molecular basis of interaction of USP7 with substrates is still under examination. One mechanism for substrate recognition is a P/AXXS motif on the substrate, recognized by USP7-NTD. This study involves two substrates, checkpoint with forkhead and ring finger domains (CHFR) and minichromosome maintenance binding protein (MCM-BP) involved with mitotic checkpoint and DNA replication, respectively. To understand the basis for interaction, co-crystal structures of USP7-NTD with CHFRPSTS and MCM-BPPSTS peptides were determined, which revealed a mechanism previously established between USP7 and p53, HDM2, HDMX and EBNA1. The peptides interacted within a shallow groove on the surface of USP7-NTD lined by residues 164DWGF167. Protein turnover assay was used to show the steady decrease of CHFR in the absence of USP7. This study has associated USP7 with DNA replication and confirmed its role at a cell cycle checkpoint.enAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.BiologyMolecular biologyBiochemistryElectronic Thesis or Dissertation2015-08-28USP7DeubiquitinationDUBStructural biologyCHFRMCM-BP