title: Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program.
abstract: The Tax oncoprotein encoded by the human T-cell leukemia virus type 1 plays a pivotal role in viral persistence and pathogenesis. Human T-cell leukemia virus type 1-infected cells proliferate faster than normal lymphocytes, expand through mitotic division, and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression, but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains, advancing their replication timing in early S phase.
authors: National Fund for Scientific Research, Gembloux Agro-Bio Tech, Cellular and Molecular Biology, University of Liège, Liège, Belgium.
authors: Mathieu
authors: M
authors: Boxus
authors: Jean-Claude
authors: JC
authors: Twizere
authors: Sébastien
authors: S
authors: Legros
authors: Richard
authors: R
authors: Kettmann
authors: Luc
authors: L
authors: Willems
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004261:DNA Replication; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005347:Fibroblasts; D005434:Flow Cytometry; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D018741:Replication Origin / Q000235:genetics*; D016196:S Phase / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D016356:Gene Products, tax; D006657:Histones; D009687:Nuclear Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2