The Architectural Chromatin Factor High Mobility Group A1 Enhances DNA Ligase IV Activity Influencing DNA Repair
| Autor: | Francesca Demarchi, Guidalberto Manfioletti, Ilenia Pellarin, Riccardo Sgarra, Silvia Costantini, Laura Arnoldo, Alessandro Vindigni, Gloria Ros, Carlotta Penzo, Gianluca Triolo, Silvia Pegoraro |
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| Přispěvatelé: | Pellarin, Ilenia, Arnoldo, Laura, Costantini, S, Pegoraro, Silvia, Ros, Gloria, Penzo, Carlotta, Triolo, G, Demarchi, F, Sgarra, Riccardo, Vindigni, A, Manfioletti, Guidalberto |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA Repair lcsh:Medicine Biochemistry Substrate Specificity Ligases Histones DNA Ligase ATP 0302 clinical medicine Cancer epigenetics HMGA1a Protein Post-Translational Modification Phosphorylation Ligation Assay lcsh:Science Chromatography High Pressure Liquid chemistry.chemical_classification Multidisciplinary biology DNA repair protein XRCC4 Recombinant Proteins Chromatin Enzymes Nucleic acids Architectural transcription factors 030220 oncology & carcinogenesis MCF-7 Cells DNA mismatch repair Comet Assay Research Article DNA repair Research and Analysis Methods Non-Homologous End Joining 03 medical and health sciences breast cancer Cell Line Tumor DNA-binding proteins Genetics Humans Molecular Biology Techniques Molecular Biology Ku Autoantigen DNA double-stranded breaks Architectural transcription factors DNA repair DNA double-stranded breaks breast cancer DNA ligase Molecular Biology Assays and Analysis Techniques lcsh:R HMGA2 Protein Biology and Life Sciences Proteins DNA Proliferating cell nuclear antigen 030104 developmental biology chemistry Microscopy Fluorescence biology.protein Cancer research Enzymology DNA damage lcsh:Q Nucleotide excision repair |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 10, p e0164258 (2016) |
| Popis: | The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. HMGA1 is a highly connected node in the nuclear molecular network and the key aspect of HMGA1 involvement in cancer development is that HMGA1 simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural and gene expression modifications up to the direct functional alterations of key cellular proteins. Interestingly, HMGA1 also modulates DNA damage repair pathways. In this work, we provide evidences linking HMGA1 with Non-Homologous End Joining DNA repair. We show that HMGA1 is in complex with and is a substrate for DNA-PK. HMGA1 enhances Ligase IV activity and it counteracts the repressive histone H1 activity towards DNA ends ligation. Moreover, breast cancer cells overexpressing HMGA1 show a faster recovery upon induction of DNA double-strand breaks, which is associated with a higher survival. These data suggest that resistance to DNA-damaging agents in cancer cells could be partially attributed to HMGA1 overexpression thus highlighting the relevance of considering HMGA1 expression levels in the selection of valuable and effective pharmacological regimens. |
| Databáze: | OpenAIRE |
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