@article{KindMusterStaroskeetal.2014,
  author    = {Kind, Barbara and Muster, Britta and Staroske, Wolfgang and Herce, Henry D. and Sachse, Rene and Rapp, Alexander and Schmidt, Franziska and Koss, Sarah and Cardoso, M. Cristina and Lee-Kirsch, Min Ae},
  title     = {Altered spatio-temporal dynamics of RNase H2 complex assembly at replication and repair sites in Aicardi-Goutieres syndrome},
  series = {Human molecular genetics},
  volume    = {23},
  journal   = {Human molecular genetics},
  number    = {22},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0964-6906},
  doi       = {10.1093/hmg/ddu319},
  pages     = {5950 -- 5960},
  year      = {2014},
  abstract  = {Ribonuclease H2 plays an essential role for genome stability as it removes ribonucleotides misincorporated into genomic DNA by replicative polymerases and resolves RNA/DNA hybrids. Biallelic mutations in the genes encoding the three RNase H2 subunits cause Aicardi-Goutieres syndrome (AGS), an early-onset inflammatory encephalopathy that phenotypically overlaps with the autoimmune disorder systemic lupus erythematosus. Here we studied the intracellular dynamics of RNase H2 in living cells during DNA replication and in response to DNA damage using confocal time-lapse imaging and fluorescence cross-correlation spectroscopy. We demonstrate that the RNase H2 complex is assembled in the cytosol and imported into the nucleus in an RNase H2B-dependent manner. RNase H2 is not only recruited to DNA replication foci, but also to sites of PCNA-dependent DNA repair. By fluorescence recovery after photobleaching, we demonstrate a high mobility and fast exchange of RNase H2 at sites of DNA repair and replication. We provide evidence that recruitment of RNase H2 is not only PCNA-dependent, mediated by an interaction of the B subunit with PCNA, but also PCNA-independent mediated via the catalytic domain of the A subunit. We found that AGS-associated mutations alter complex formation, recruitment efficiency and exchange kinetics at sites of DNA replication and repair suggesting that impaired ribonucleotide removal contributes to AGS pathogenesis.},
  language  = {en}
}
@article{WuHanRodriguezSillkeetal.2019,
  author    = {Wu, Hao and Han, Yijie and Rodriguez Sillke, Yasmina and Deng, Hongzhang and Siddiqui, Sophiya and Treese, Christoph and Schmidt, Franziska and Friedrich, Marie and Keye, Jacqueline and Wan, Jiajia and Qin, Yue and K{\"u}hl, Anja A. and Qin, Zhihai and Siegmund, Britta and Glauben, Rainer},
  title     = {Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages},
  series = {EMBO molecular medicine},
  volume    = {11},
  journal   = {EMBO molecular medicine},
  number    = {11},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1757-4676},
  doi       = {10.15252/emmm.201910698},
  pages     = {17},
  year      = {2019},
  abstract  = {Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.},
  language  = {en}
}