title: Role for Plk1 phosphorylation of Hbo1 in regulation of replication licensing.
abstract: In a search for Polo-like kinase 1 (Plk1)-interacting proteins using a yeast two-hybrid system, we have identified histone acetyltransferase binding to the origin recognition complex 1 (Hbo1) as a potential Plk1 target. Here, we show that the interaction between Plk1 and Hbo1 is mitosis-specific and that Plk1 phosphorylates Hbo1 on Ser-57 in vitro and in vivo. During mitosis, Cdk1 phosphorylates Hbo1 on Thr-85/88, creating a docking site for Plk1 to be recruited. Significantly, the overexpression of Hbo1 mutated at the Plk1 phosphorylation site (S57A) leads to cell-cycle arrest in the G1/S phase, inhibition of chromatin loading of the minichromosome maintenance (Mcm) complex, and a reduced DNA replication rate. Similarly, Hbo1 depletion results in decreased DNA replication and a failure of Mcm complex binding to chromatin, both of which can be partially rescued by the ectopic expression of WT Hbo1 but not Hbo1-S57A. These results suggest that Plk1 phosphorylation of Hbo1 may be required for prereplicative complex (pre-RC) formation and DNA replication licensing.
authors.affiliation: Department of Biochemistry and Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Zhao-Qiu
authors.initials: ZQ
authors.lastname: Wu
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D004261:DNA Replication / Q000502:physiology*; D016193:G1 Phase; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D016196:S Phase; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D051548:Histone Acetyltransferases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C496553:KAT7 protein, human