title: Neurodegeneration-associated instability of ribosomal DNA.
abstract: Homologous recombination (HR)-mediated instability of the repetitively organized ribosomal DNA (rDNA) has been proposed as a mediator of cell senescence in yeast triggering the DNA damage response. High individual variability in the content of human rDNA suggests that this genomic region remained relatively unstable throughout evolution. Therefore, quantitative real-time polymerase chain reaction was used to determine the genomic content of rDNA in post mortem samples of parietal cortex from 14 young and 9 elderly individuals with no diagnosis of a chronic neurodegenerative/neurological disease. In addition, rDNA content in that brain region was compared between 10 age-matched control individuals and 10 patients with dementia with Lewy bodies (DLB) which involves neurodegeneration of the cerebral cortex. Probing rRNA-coding regions of rDNA revealed no effects of aging on the rDNA content. Elevated rDNA content was observed in DLB. Conversely, in the DLB pathology-free cerebellum, lower genomic content of rDNA was present in the DLB group. In the parietal cortex, such a DLB-associated instability of rDNA was not accompanied by any major changes of cytosine-phosphate-guanine methylation of the rDNA promoter. As increased cerebro-cortical rDNA content was previously reported in Alzheimer's disease, neurodegeneration appears to be associated with instability of rDNA. The hypothetical origins and consequences of this phenomenon are discussed including possibilities that the DNA damage-induced recombination destabilizes rDNA and that differential content of rDNA affects heterochromatin formation, gene expression and/or DNA damage response. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
authors.affiliation: Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40292, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY 40292, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hallgren
authors.affiliation: Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40292, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pietrzak
authors.affiliation: Division of Biostatistics, College of Public Health, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rempala
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.affiliation: Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY 40292, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY 40292, USA; Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY 40292, USA. Electronic address: michal.hetman@louisville.edu.
authors.forename: Michal
authors.initials: M
authors.lastname: Hetman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D016922:Cellular Senescence / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D004249:DNA Damage / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics*; D005260:Female; D042822:Genomic Instability; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000473:pathology; D020961:Lewy Body Disease / Q000235:genetics* / Q000503:physiopathology; D008297:Male
chemical_list: D004275:DNA, Ribosomal
keywords: Aging; Dementia with Lewy bodies; Genomic instability; Neurodegeneration; Nucleolus