S100A11 plays a role in homologous recombination and genome maintenance by influencing the persistence of RAD51 in DNA repair foci
| Autor: | Helmut Pospiech, Florian Kraft, Alexandra Zielinski, Anja Weise, Kerstin Borgmann, Bernhard Schlott, Kristin Mrasek, Franziska Foertsch, Anna Szambowska, Christian Melle, Frank Grosse |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA Repair DNA repair Cell Survival RAD51 Down-Regulation Biology Cell Line Homology directed repair 03 medical and health sciences 0302 clinical medicine Report Humans Homologous Recombination Molecular Biology Replication protein A Chromosome Aberrations Genome Human S100 Proteins Cell Biology DNA repair protein XRCC4 Molecular biology Non-homologous end joining 030104 developmental biology 030220 oncology & carcinogenesis Gene Knockdown Techniques DNA mismatch repair Calcium Mutant Proteins Rad51 Recombinase Developmental Biology Nucleotide excision repair DNA Damage Protein Binding |
| Popis: | 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 Ca2+, 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. |
| Databáze: | OpenAIRE |
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