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Identification and characterization of human holocarboxylase synthetase/protein interactions at the molecular level

Yousef Ismail Hassan, University of Nebraska - Lincoln

Abstract

Covalent modifications of histones are a crucial component of epigenetic events that regulate chromatin structures and gene function. Evidence exists that distinct lysine residues in histones are modified by covalent attachment of the vitamin biotin. More than 11 distinct lysine residues have been identified as possible targets for biotinylation including K9, K13, K125, K127, and K129 in histone H2A; K4, K9, and K18 and perhaps K23 in histone H3; and K8 and K12 in histone H4. Biotinylated histones participate in gene silencing, mitotic condensation of chromatin, and the cellular response to DNA damage. The major enzyme responsible for histone biotinylation is, holocarboxylase synthetase (HCS). While the nuclear translocation of this enzyme is confirmed, the mechanism of this translocation is still ambiguous. This 726 amino acid protein lacks a classical nuclear localization sequence (NLS) and DNA-binding motif. It has been proposed that HCS-interacting proteins mediate the nuclear translocation and chromosome binding of HCS. This thesis focuses on the identification and molecular characterization of holocarboxylase synthetase protein interactions. Here, we provide evidence that both N- and C-termini in HCS are involved in substrate recognition; show that HCS interacts with a 67 amino acids long polypeptide indentified in Y2H assays, offering novel insights into the protein biotinylation mechanism; and finally report a possible interaction between the euchromatic histone methyltransferase-1 (EHMT-1) protein and HCS.^

Subject Area

Biology, Molecular|Chemistry, Biochemistry|Health Sciences, Nutrition

Recommended Citation

Hassan, Yousef Ismail, "Identification and characterization of human holocarboxylase synthetase/protein interactions at the molecular level" (2009). ETD collection for University of Nebraska - Lincoln. AAI3359465.
http://digitalcommons.unl.edu/dissertations/AAI3359465

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