Characterization of the major formamidopyrimidine-DNA glycosylase homolog inMycobacterium tuberculosisand its linkage to variable tandem repeats
| Autor: | Einar Andreas Rødland, Seetha V. Balasingham, Tone Tønjum, Ingrun Alseth, Ingrid Olsen, Dick van Soolingen, Kristin Kremer, Tonje Davidsen, Ephrem Debebe |
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| Rok vydání: | 2009 |
| Předmět: |
DNA
Bacterial Microbiology (medical) DNA Repair DNA damage DNA repair Immunology Gene Expression Sequence Homology formamidopyrimidine–DNA glycosylase Minisatellite Repeats Microbiology Substrate Specificity Mycobacterium tuberculosis chemistry.chemical_compound Bacterial Proteins Tandem repeat Humans Immunology and Allergy Conserved Sequence Research Articles biology Gene Expression Profiling General Medicine Formamidopyrimidine DNA glycosylase biology.organism_classification Molecular biology tandem repeats Variable number tandem repeat Infectious Diseases DNA-Formamidopyrimidine Glycosylase chemistry Biochemistry DNA glycosylase DNA |
| Zdroj: | Fems Immunology and Medical Microbiology |
| ISSN: | 1574-695X 0928-8244 |
| DOI: | 10.1111/j.1574-695x.2009.00562.x |
| Popis: | The ability to repair DNA damage is likely to play an important role in the survival of facultative intracellular parasites because they are exposed to high levels of reactive oxygen species and nitrogen intermediates inside phagocytes. Correcting oxidative damage in purines and pyrimidines is the primary function of the enzymes formamidopyrimidine (faPy)–DNA glycosylase (Fpg) and endonuclease VIII (Nei) of the base excision repair pathway, respectively. Four gene homologs, belonging to the fpg/nei family, have been identified in Mycobacterium tuberculosis H37Rv. The recombinant protein encoded by M. tuberculosis Rv2924c, termed Mtb-Fpg1, was overexpressed, purified and biochemically characterized. The enzyme removed faPy and 5-hydroxycytosine lesions, as well as 8-oxo-7,8-dihydroguanine (8oxoG) opposite to C, T and G. Mtb-Fpg1 thus exhibited substrate specificities typical for Fpg enzymes. Although Mtb-fpg1 showed nearly complete nucleotide sequence conservation in 32 M. tuberculosis isolates, the region upstream of Mtb-fpg1 in these strains contained tandem repeat motifs of variable length. A relationship between repeat length and Mtb-fpg1 expression level was demonstrated in M. tuberculosis strains, indicating that an increased length of the tandem repeats positively influenced the expression levels of Mtb-fpg1. This is the first example of such a tandem repeat region of variable length being linked to the expression level of a bacterial gene. |
| Databáze: | OpenAIRE |
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