TY  - JOUR
A1  - Wanzek, Katharina
A1  - Schwindt, Eike
A1  - Capra, John A.
A1  - Paeschke, Katrin
T1  - Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability
JF  - Nucleic Acids Research
N2  - The regulation of replication is essential to preserve genome integrity. Mms1 is part of the E3 ubiquitin ligase complex that is linked to replication fork progression. By identifying Mms1 binding sites genome-wide in Saccharomyces cerevisiae we connected Mms1 function to genome integrity and replication fork progression at particular G-rich motifs. This motif can form G-quadruplex (G4) structures in vitro. G4 are stable DNA structures that are known to impede replication fork progression. In the absence of Mms1, genome stability is at risk at these G-rich/G4 regions as demonstrated by gross chromosomal rearrangement assays. Mms1 binds throughout the cell cycle to these G-rich/G4 regions and supports the binding of Pif1 DNA helicase. Based on these data we propose a mechanistic model in which Mms1 binds to specific G-rich/G4 motif located on the lagging strand template for DNA replication and supports Pif1 function, DNA replication and genome integrity.
KW  - replication
KW  - regulation
KW  - genome integrity
KW  - Saccharomyces cerevisiae
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170577
VL  - 45
IS  - 13
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  -