title: Genomic instability associated with myotonic dystrophy does not involve p53 expression and activity.
abstract: We tested the hypothesis that the instability of the trinucleotide CTG at the myotonic dystrophy (DM) locus could be an intrinsic DNA damage recognisable by the p53 cell-cycle checkpoint system. p53 mRNA and protein levels were assayed in muscle biopsies and fibroblast cell lines of DM patients and unaffected controls. No differences in mRNA and protein levels were found between patients and controls, regardless of their expansion size. However, in the cells treated with adryamicin, p53 protein levels were comparable in DM and control cells. We conclude that the CTG trinucleotide expansion within the myotonin gene does not activate the p53 surveillance system, at least in adult tissues. The escape of trinucleotide expansion from the p53-mediated DNA repair system could explain some of the biological characteristics of genome instability.
authors.affiliation: Department of Public Health and Cell Biology, Tor Vergata University, Rome, Italy. gennarelli@utovrm.it
authors.forename: M
authors.initials: M
authors.lastname: Gennarelli
authors.forename: M
authors.initials: M
authors.lastname: Lucarelli
authors.forename: P
authors.initials: P
authors.lastname: Amicucci
authors.forename: S
authors.initials: S
authors.lastname: Soddu
authors.forename: G
authors.initials: G
authors.lastname: Novelli
authors.forename: B
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D016158:Genes, p53; D015894:Genome, Human; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D009223:Myotonic Dystrophy / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D018911:Trinucleotide Repeats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53