@article{PhillipsChanPaeschkeetal.2015,
  author    = {Phillips, Jane A. and Chan, Angela and Paeschke, Katrin and Zakian, Virginia A.},
  title     = {The Pif1 helicase, a negative regulator of telomerase, acts preferentially at long telomeres},
  series = {PLoS Genetics},
  volume    = {11},
  journal   = {PLoS Genetics},
  number    = {4},
  doi       = {10.1371/journal.pgen.1005186},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148722},
  pages     = {e1005186},
  year      = {2015},
  abstract  = {Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The S. cerevisiae Pif1 DNA helicase inhibits both telomerase-mediated telomere lengthening and de novo telomere addition at double strand breaks (DSB). Here, we report that the association of the telomerase subunits Est2 and Est1 at a DSB was increased in the absence of Pif1, as it is at telomeres, suggesting that Pif1 suppresses de novo telomere addition by removing telomerase from the break. To determine how the absence of Pif1 results in telomere lengthening, we used the single telomere extension assay (STEX), which monitors lengthening of individual telomeres in a single cell cycle. In the absence of Pif1, telomerase added significantly more telomeric DNA, an average of 72 nucleotides per telomere compared to the 45 nucleotides in wild type cells, and the fraction of telomeres lengthened increased almost four-fold. Using an inducible short telomere assay, Est2 and Est1 no longer bound preferentially to a short telomere in pif1 mutant cells while binding of Yku80, a telomere structural protein, was unaffected by the status of the PIF1 locus. Two experiments demonstrate that Pif1 binding is affected by telomere length: Pif1 (but not Yku80) -associated telomeres were 70 bps longer than bulk telomeres, and in the inducible short telomere assay, Pif1 bound better to wild type length telomeres than to short telomeres. Thus, preferential lengthening of short yeast telomeres is achieved in part by targeting the negative regulator Pif1 to long telomeres.},
  language  = {en}
}
@article{WanzekSchwindtCapraetal.2017,
  author    = {Wanzek, Katharina and Schwindt, Eike and Capra, John A. and Paeschke, Katrin},
  title     = {Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability},
  series = {Nucleic Acids Research},
  volume    = {45},
  journal   = {Nucleic Acids Research},
  number    = {13},
  doi       = {10.1093/nar/gkx467},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170577},
  pages     = {7796-7806},
  year      = {2017},
  abstract  = {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.},
  language  = {en}
}
@article{SauerJuranekMarksetal.2019,
  author    = {Sauer, Markus and Juranek, Stefan A. and Marks, James and De Magis, Alessio and Kazemier, Hinke G and Hilbig, Daniel and Benhalevy, Daniel and Wang, Xiantao and Hafner, Markus and Paeschke, Katrin},
  title     = {DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  number    = {2421},
  doi       = {10.1038/s41467-019-10432-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227486},
  pages     = {1-15},
  year      = {2019},
  abstract  = {Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.},
  language  = {en}
}
@article{BenhalevyGuptaDananetal.2017,
  author    = {Benhalevy, Daniel and Gupta, Sanjay K. and Danan, Charles H. and Ghosal, Suman and Sun, Hong-Wei and Kazemeier, Hinke G. and Paeschke, Katrin and Hafner, Markus and Juranek, Stefan A.},
  title     = {The Human CCHC-type Zinc Finger Nucleic Acid-Binding Protein Binds G-Rich Elements in Target mRNA Coding Sequences and Promotes Translation},
  series = {Cell Reports},
  volume    = {18},
  journal   = {Cell Reports},
  number    = {12},
  doi       = {10.1016/j.celrep.2017.02.080},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171122},
  pages     = {2979-2990},
  year      = {2017},
  abstract  = {The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs. CNBP preferentially bound G-rich elements in the target mRNA coding sequences, most of which were previously found to form G-quadruplex and other stable structures in vitro. Functional analyses, including RNA sequencing, ribosome profiling, and quantitative mass spectrometry, revealed that CNBP binding did not influence target mRNA abundance but rather increased their translational efficiency. Considering that CNBP binding prevented G-quadruplex structure formation in vitro, we hypothesize that CNBP is supporting translation by resolving stable structures on mRNAs.},
  language  = {en}
}