Self-catalytic DNA Depurination Underlies Human β-Globin Gene Mutations at Codon 6 That Cause Anemias and Thalassemias. Alvarez-Dominguez, J. R., Amosova, O., & Fresco, J. R. Journal of Biological Chemistry, 288(16):11581–11589, April, 2013. MAG ID: 1965380434
doi  abstract   bibtex   
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.
@article{alvarez-dominguez_self-catalytic_2013,
	title = {Self-catalytic {DNA} {Depurination} {Underlies} {Human} β-{Globin} {Gene} {Mutations} at {Codon} 6 {That} {Cause} {Anemias} and {Thalassemias}},
	volume = {288},
	doi = {10.1074/jbc.m113.454744},
	abstract = {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.},
	number = {16},
	journal = {Journal of Biological Chemistry},
	author = {Alvarez-Dominguez, Juan R. and Amosova, Olga and Fresco, Jacques R.},
	month = apr,
	year = {2013},
	doi = {10.1074/jbc.m113.454744},
	pmcid = {3630879},
	pmid = {23457306},
	note = {MAG ID: 1965380434},
	pages = {11581--11589},
}

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