title: DNA-protein interaction dynamics at the Lamin B2 replication origin.
abstract: To date, a complete understanding of the molecular events leading to DNA replication origin activation in mammalian cells still remains elusive. In this work, we report the results of a high resolution chromatin immunoprecipitation study to detect proteins interacting with the human Lamin B2 replication origin. In addition to the pre-RC component ORC4 and to the transcription factors USF and HOXC13, we found that 2 components of the AP-1 transcription factor, c-Fos and c-Jun, are also associated with the origin DNA during the late G1 phase of the cell cycle and that these factors interact with ORC4. Both DNA replication and AP-1 factor binding to the origin region were perturbed by cell treatment with merbarone, a topoisomerase II inhibitor, suggesting that DNA topology is essential for determining origin function.
authors.affiliation: a Molecular Biology Laboratory; Scuola Normale Superiore ; Pisa , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Puzzi
authors.forename: Laura
authors.initials: L
authors.lastname: Marchetti
authors.forename: Fiorenzo A
authors.initials: FA
authors.lastname: Peverali
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biamonti
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D016193:G1 Phase; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D051738:Origin Recognition Complex / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018741:Replication Origin / Q000187:drug effects; D013858:Thiobarbiturates / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051720:Upstream Stimulatory Factors / Q000378:metabolism
chemical_list: C410305:HOXC13 protein, human; D018398:Homeodomain Proteins; D034921:Lamin Type B; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D051738:Origin Recognition Complex; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C485737:TIMM13 protein, human; D013858:Thiobarbiturates; D059005:Topoisomerase II Inhibitors; D018808:Transcription Factor AP-1; D051720:Upstream Stimulatory Factors; D004247:DNA; C045459:merbarone
keywords: AP-1; DNA replication origin; Fos; Jun; origin recognition complex; transcription factor