title: S100A11 plays a role in homologous recombination and genome maintenance by influencing the persistence of RAD51 in DNA repair foci.
abstract: The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is an essential process in maintenance of chromosomal stability. A key player of HR is the strand exchange factor RAD51 whose assembly at sites of DNA damage is tightly regulated. We detected an endogenous complex of RAD51 with the calcium-binding protein S100A11, which is localized at sites of DNA repair in HaCaT cells as well as in normal human epidermal keratinocytes (NHEK) synchronized in S phase. In biochemical assays, we revealed that S100A11 enhanced the RAD51 strand exchange activity. When cells expressing a S100A11 mutant lacking the ability to bind Ca(2+), a prolonged persistence of RAD51 in repair sites and nuclear γH2AX foci was observed suggesting an incomplete DNA repair. The same phenotype became apparent when S100A11 was depleted by RNA interference. Furthermore, down-regulation of S100A11 resulted in both reduced sister chromatid exchange confirming the restriction of the recombination capacity of the cells, and in an increase of chromosomal aberrations reflecting the functional requirement of S100A11 for the maintenance of genomic stability. Our data indicate that S100A11 is involved in homologous recombination by regulating the appearance of RAD51 in DSB repair sites. This function requires the calcium-binding activity of S100A11.
authors: a Biomolecular Photonics Group , Jena University Hospital , Jena , Germany.
authors: Franziska
authors: F
authors: Foertsch
authors: b Research Group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute , Jena , Germany.
authors: Anna
authors: A
authors: Szambowska
authors: c Institute of Human Genetics , Jena University Hospital , Jena , Germany.
authors: Anja
authors: A
authors: Weise
authors: d Radiobiology & Experimental Radiooncology , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors: Alexandra
authors: A
authors: Zielinski
authors: b Research Group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute , Jena , Germany.
authors: Bernhard
authors: B
authors: Schlott
authors: c Institute of Human Genetics , Jena University Hospital , Jena , Germany.
authors: Florian
authors: F
authors: Kraft
authors: c Institute of Human Genetics , Jena University Hospital , Jena , Germany.
authors: Kristin
authors: K
authors: Mrasek
authors: d Radiobiology & Experimental Radiooncology , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors: Kerstin
authors: K
authors: Borgmann
authors: b Research Group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute , Jena , Germany.|e Faculty of Biochemistry and Molecular Medicine , University of Oulu , Finland.
authors: Helmut
authors: H
authors: Pospiech
authors: b Research Group Biochemistry, Leibniz Institute on Aging - Fritz Lipmann Institute , Jena , Germany.
authors: Frank
authors: F
authors: Grosse
authors: a Biomolecular Photonics Group , Jena University Hospital , Jena , Germany.
authors: Christian
authors: C
authors: Melle
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D015894:Genome, Human; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D051135:Rad51 Recombinase / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D009418:S100 Proteins; C072337:S100A11 protein, human; D051135:Rad51 Recombinase; D002118:Calcium
keywords: DNA double-strand breaks; RAD51; S100A11; genomic aberrations; homogenous recombination