TY  - JOUR
A1  - Reis, Helena
A1  - Schwebs, Marie
A1  - Dietz, Sabrina
A1  - Janzen, Christian J.
A1  - Butter, Falk
T1  - TelAP1 links telomere complexes with developmental expression site silencing in African trypanosomes
JF  - Nucleic Acids Research
N2  - During its life cycle, Trypanosoma brucei shuttles between a mammalian host and the tsetse fly vector. In the mammalian host, immune evasion of T. brucei bloodstream form (BSF) cells relies on antigenic variation, which includes monoallelic expression and periodic switching of variant surface glycoprotein (VSG) genes. The active VSG is transcribed from only 1 of the 15 subtelomeric expression sites (ESs). During differentiation from BSF to the insect-resident procyclic form (PCF), the active ES is transcriptionally silenced. We used mass spectrometry-based interactomics to determine the composition of telomere protein complexes in T. brucei BSF and PCF stages to learn more about the structure and functions of telomeres in trypanosomes. Our data suggest a different telomere complex composition in the two forms of the parasite. One of the novel telomere-associated proteins, TelAP1, forms a complex with telomeric proteins TbTRF, TbRAP1 and TbTIF2 and influences ES silencing kinetics during developmental differentiation.
KW  - Gene Regulation
KW  - Chromatin and Epigenetics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225180
VL  - 46
IS  - 6
ER  - 
TY  - JOUR
A1  - Leal, Andrea Zurita
A1  - Schwebs, Marie
A1  - Briggs, Emma
A1  - Weisert, Nadine
A1  - Reis, Helena
A1  - Lemgruber, Leondro
A1  - Luko, Katarina
A1  - Wilkes, Jonathan
A1  - Butter, Falk
A1  - McCulloch, Richard
A1  - Janzen, Christian J.
T1  - Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation
JF  - Nucleic Acids Research
N2  - Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to off-spring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.
KW  - cross-link repair
KW  - cell cycle
KW  - gene expression
KW  - low fidelity
KW  - replication
KW  - bypass
KW  - theta
KW  - reveals
KW  - binding
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230579
VL  - 48
IS  - 17
ER  -