A model for systemic lupus erythematosus based on chromatin disruption by polyamines.
Here it is hypothesized that some autoimmune disorders, such as systemic lupus erythematosus, result in part from overexpression of polyamines which leads to disruption of chromatin structure. Disruption of inactive chromatin, such as the inactive X chromosome, exposes sites of unrepaired DNA damage. Repair is then hampered by the polyamines. Disruption also facilitates transcription at previously sequestered sites. Especially interesting are RNA polymerase III sites in highly repeated sequences such as the Alu sequence. Transcription and translation from these sites could create RNA and polypeptides not normally expressed. These could be antigenic either individually or in association with other cellular components. Interactions of polyamines in the nucleus and with the membrane could also lead to polyamine facilitated apoptosis.
Brooks
W H
WH
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226, USA.
D000974:Antibodies, Antinuclear / Q000276:immunology*; D000918:Antibody Specificity; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D004247:DNA / Q000235:genetics / Q000276:immunology; D004249:DNA Damage; D004260:DNA Repair; D004251:DNA Transposable Elements / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008954:Models, Biological; D009707:Nucleosomes / Q000648:ultrastructure; D009955:Ornithine Decarboxylase / Q000502:physiology; D011073:Polyamines / Q000378:metabolism*; D012320:RNA Polymerase III / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D012737:Sex Factors; D014158:Transcription, Genetic
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D002843:Chromatin; D004251:DNA Transposable Elements; D009707:Nucleosomes; D011073:Polyamines; D004247:DNA; D012320:RNA Polymerase III; D009955:Ornithine Decarboxylase