Self-catalytic DNA Depurination Underlies Human β-Globin Gene Mutations at Codon 6 That Cause Anemias and Thalassemias
| Autor: | Olga Amosova, Jacques R. Fresco, Juan R. Alvarez-Dominguez |
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| Rok vydání: | 2013 |
| Předmět: |
Silent mutation
endocrine system beta-Globins Biology medicine.disease_cause Biochemistry hemic and lymphatic diseases medicine Animals Humans AP site Codon Molecular Biology Gene Genetics Mutation fungi food and beverages Anemia Molecular Bases of Disease DNA Cell Biology Molecular biology Coding strand Codon usage bias Nucleic Acid Conformation Thalassemia Depurination Synonymous substitution |
| Zdroj: | Journal of Biological Chemistry. 288:11581-11589 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m113.454744 |
| Popis: | The human β-globin gene contains an 18-nucleotide coding strand sequence centered at codon 6 and capable of forming a stem-loop structure that can self-catalyze depurination of the 5'G residue of that codon. The resultant apurinic lesion is subject to error-prone repair, consistent with the occurrence about this codon of mutations responsible for 6 anemias and β-thalassemias and additional substitutions without clinical consequences. The 4-residue loop of this stem-loop-forming sequence shows the highest incidence of mutation across the gene. The loop and first stem base pair-forming residues appeared early in the mammalian clade. The other stem-forming segments evolved more recently among primates, thereby conferring self-depurination capacity at codon 6. These observations indicate a conserved molecular mechanism leading to β-globin variants underlying phenotypic diversity and disease. |
| Databáze: | OpenAIRE |
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