title: DNA damage-induced translocation of S100A11 into the nucleus regulates cell proliferation.
abstract: BACKGROUND
  Proteins are able to react in response to distinct stress stimuli by alteration of their subcellular distribution. The stress-responsive protein S100A11 belongs to the family of multifunctional S100 proteins which have been implicated in several key biological processes. Previously, we have shown that S100A11 is directly involved in DNA repair processes at damaged chromatin in the nucleus. To gain further insight into the underlying mechanism subcellular trafficking of S100A11 in response to DNA damage was analyzed.
  
  
  RESULTS
  We show that DNA damage induces a nucleolin-mediated translocation of S100A11 from the cytoplasm into the nucleus. This translocation is impeded by inhibition of the phosphorylation activity of PKCα. Translocation of S100A11 into the nucleus correlates with an increased cellular p21 protein level. Depletion of nucleolin by siRNA severely impairs translocation of S100A11 into the nucleus resulting in a decreased p21 protein level. Additionally, cells lacking nucleolin showed a reduced colony forming capacity.
  
  
  CONCLUSIONS
  These observations suggest that regulation of the subcellular distribution of S100A11 plays an important role in the DNA damage response and p21-mediated cell cycle control.
authors.affiliation: Institute of Human Genetics and Anthropology, University Hospital Jena, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Gorsler
authors.forename: Ulrike
authors.initials: U
authors.lastname: Murzik
authors.forename: Tobias
authors.initials: T
authors.lastname: Ulbricht
authors.forename: Julia
authors.initials: J
authors.lastname: Hentschel
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmerich
authors.forename: Christian
authors.initials: C
authors.lastname: Melle
mesh_terms: D021581:Active Transport, Cell Nucleus; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051571:Protein Kinase C-alpha; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010750:Phosphoproteins; D051571:Protein Kinase C-alpha; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D009418:S100 Proteins; D000097796:Nucleolin; C072337:S100A11 protein, human