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  - Lüningschrör, Patrick
A1  - Binotti, Beyenech
A1  - Dombert, Benjamin
A1  - Heimann, Peter
A1  - Perez-Lara, Angel
A1  - Slotta, Carsten
A1  - Thau-Habermann, Nadine
A1  - von Collenberg, Cora R.
A1  - Karl, Franziska
A1  - Damme, Markus
A1  - Horowitz, Arie
A1  - Maystadt, Isabelle
A1  - Füchtbauer, Annette
A1  - Füchtbauer, Ernst-Martin
A1  - Jablonka, Sibylle
A1  - Blum, Robert
A1  - Üçeyler, Nurcan
A1  - Petri, Susanne
A1  - Kaltschmidt, Barbara
A1  - Jahn, Reinhard
A1  - Kaltschmidt, Christian
A1  - Sendtner, Michael
T1  - Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease
JF  - Nature Communications
N2  - Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease.
KW  - autophagy
KW  - synaptic vesicles
KW  - Pleckstrin homology containing family member 5 (Plekhg5)
KW  - regulation
KW  - motoneuron disease
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170048
VL  - 8
IS  - 678
ER  -