TY  - JOUR
A1  - Gassen, Alwine
A1  - Brechtefeld, Doris
A1  - Schandry, Niklas
A1  - Arteaga-Salas, J. Manuel
A1  - Israel, Lars
A1  - Imhof, Axel
A1  - Janzen, Christian J.
T1  - DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei
JF  - Nucleic Acids Research
N2  - 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-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.
KW  - variants
KW  - cell-cycle regulation
KW  - blood-stream forms
KW  - african trypanosomes
KW  - mammalian cells
KW  - DNA replication
KW  - DOT1
KW  - protein
KW  - transcription
KW  - cultivation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131449
VL  - 40
IS  - 20
ER  - 
TY  - JOUR
A1  - Weiße, Sebastian
A1  - Heddergott, Niko
A1  - Heydt, Matthias
A1  - Pflästerer, Daniel
A1  - Maier, Timo
A1  - Haraszti, Tamas
A1  - Grunze, Michael
A1  - Engstler, Markus
A1  - Rosenhahn, Axel
T1  - A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy
JF  - PLoS One
N2  - We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming.
KW  - african trypanosomes
KW  - actin cortex
KW  - flagellum
KW  - tracking
KW  - surface
KW  - models
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130666
VL  - 7
IS  - 5
ER  - 
TY  - JOUR
A1  - Pascoalino, Bruno
A1  - Dindar, Gülcin
A1  - Vieira-da-Rocha, João P.
A1  - Machado, Carlos Renato
A1  - Janzen, Christian J.
A1  - Schenkman, Sergio
T1  - Characterization of two different Asf1 histone chaperones with distinct cellular localizations and functions in Trypanosoma brucei
JF  - Nucleic Acids Research
N2  - The anti-silencing function protein 1 (Asf1) is a chaperone that forms a complex with histones H3 and H4 facilitating dimer deposition and removal from chromatin. Most eukaryotes possess two different Asf1 chaperones but their specific functions are still unknown. Trypanosomes, a group of early-diverged eukaryotes, also have two, but more divergent Asf1 paralogs than Asf1 of higher eukaryotes. To unravel possible different functions, we characterized the two Asf1 proteins in Trypanosoma brucei. Asf1A is mainly localized in the cytosol but translocates to the nucleus in S phase. In contrast, Asf1B is predominantly localized in the nucleus, as described for other organisms. Cytosolic Asf1 knockdown results in accumulation of cells in early S phase of the cell cycle, whereas nuclear Asf1 knockdown arrests cells in S/G2 phase. Overexpression of cytosolic Asf1 increases the levels of histone H3 and H4 acetylation. In contrast to cytosolic Asf1, overexpression of nuclear Asf1 causes less pronounced growth defects in parasites exposed to genotoxic agents, prompting a function in chromatin remodeling in response to DNA damage. Only the cytosolic Asf1 interacts with recombinant H3/H4 dimers in vitro. These findings denote the early appearance in evolution of distinguishable functions for the two Asf1 chaperons in trypanosomes.
KW  - chromatin assembly factors
KW  - DNA-damage checkpoint
KW  - tousled-like kinases
KW  - saccharomyes cerevisiae
KW  - gene expression
KW  - acetyltransferase RTT109
KW  - african trypanosomes
KW  - antigenetic variation
KW  - cycle regulation
KW  - nuclear import
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117220
SN  - 1362-4962
VL  - 42
IS  - 5
ER  -