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DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei

Please always quote using this URN: urn:nbn:de:bvb:20-opus-131449
  • Cell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. Although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite Trypanosoma brucei, novel regulatory mechanisms seem to have evolved. Here, we analyse the function of the histone methyltransferase DOT1A during cell-cycle progression. Over-expression of DOT1A generates a population of cells with aneuploid nuclei as well as enucleated cells. Detailed analysis shows that DOT1A over-expressionCell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. Although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite Trypanosoma brucei, novel regulatory mechanisms seem to have evolved. Here, we analyse the function of the histone methyltransferase DOT1A during cell-cycle progression. Over-expression of DOT1A generates a population of cells with aneuploid nuclei as well as enucleated cells. Detailed analysis shows that DOT1A over-expression causes continuous replication of the nuclear DNA. In contrast, depletion of DOT1A by RNAi abolishes replication but does not prevent karyokinesis. As histone H3K76 methylation has never been associated with replication control in eukaryotes before, we have discovered a novel function of DOT1 enzymes, which might not be unique to trypanosomes.show moreshow less

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Metadaten
Author: Alwine Gassen, Doris Brechtefeld, Niklas Schandry, J. Manuel Arteaga-Salas, Lars Israel, Axel Imhof, Christian J. Janzen
URN:urn:nbn:de:bvb:20-opus-131449
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Nucleic Acids Research
Year of Completion:2012
Volume:40
Issue:20
Pagenumber:10302 - 10311
Source:Nucleic Acids Research, 2012, Vol. 40, No. 20, pp. 10302–10311. doi:10.1093/nar/gks801
DOI:https://doi.org/10.1093/nar/gks801
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:DNA replication; DOT1; african trypanosomes; blood-stream forms; cell-cycle regulation; cultivation; mammalian cells; protein; transcription; variants
Release Date:2016/12/13
Licence (German):License LogoCC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell