The helicase DinG responds to stress due to DNA double strand breaks
| Autor: | Tahira Riaz, Amine Namouchi, Marta Gómez-Muñoz, Håvard Homberset, Stephan A. Frye, Seetha V. Balasingham, Getachew Tesfaye Beyene, Shewit Kalayou, Tone Tønjum |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular Adenosine Triphosphatase 0301 basic medicine Genome instability lcsh:Medicine Neisseria meningitidis Biochemistry Database and Informatics Methods chemistry.chemical_compound DNA metabolism DNA Breaks Double-Stranded lcsh:Science Phylogeny Polymerase Multidisciplinary biology Gene Expression Regulation Developmental Enzymes Nucleic acids Helicases Sequence Analysis Research Article DNA Bacterial Bioinformatics DNA repair DNA damage Mitomycin 030106 microbiology DNA replication Research and Analysis Methods Genomic Instability 03 medical and health sciences Bacterial Proteins Sequence Motif Analysis DNA-binding proteins Genetics Molecular Biology Techniques Molecular Biology RecBCD lcsh:R DNA Helicases Phosphatases Biology and Life Sciences Proteins Helicase DNA Vector Cloning Molecular biology Protein Structure Tertiary chemistry Enzymology biology.protein lcsh:Q Cloning |
| Zdroj: | PLoS ONE, Vol 12, Iss 11, p e0187900 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Neisseria meningitidis (Nm) is a Gram-negative nasopharyngeal commensal that can cause septicaemia and meningitis. The neisserial DNA damage-inducible protein DinG is a helicase related to the mammalian helicases XPD and FANCJ. These helicases belong to superfamily 2, are ATP dependent and exert 5′ → 3′ directionality. To better understand the role of DinG in neisserial genome maintenance, the Nm DinG (DinGNm) enzymatic activities were assessed in vitro and phenotypical characterization of a dinG null mutant (NmΔdinG) was performed. Like its homologues, DinGNm possesses 5′ → 3′ directionality and prefers DNA substrates containing a 5′-overhang. ATPase activity of DinGNm is strictly DNA-dependent and DNA unwinding activity requires nucleoside triphosphate and divalent metal cations. DinGNm directly binds SSBNm with a Kd of 313 nM. Genotoxic stress analysis demonstrated that NmΔdinG was more sensitive to double-strand DNA breaks (DSB) induced by mitomycin C (MMC) than the Nm wildtype, defining the role of neisserial DinG in DSB repair. Notably, when NmΔdinG cells grown under MMC stress assessed by quantitative mass spectrometry, 134 proteins were shown to be differentially abundant (DA) compared to unstressed NmΔdinG cells. Among the DNA replication, repair and recombination proteins affected, polymerase III subunits and recombinational repair proteins RuvA, RuvB, RecB and RecD were significantly down regulated while TopA and SSB were upregulated under stress condition. Most of the other DA proteins detected are involved in metabolic functions. The present study shows that the helicase DinG is probably involved in regulating metabolic pathways as well as in genome maintenance. |
| Databáze: | OpenAIRE |
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