title: [Mosaic forms of ataxia-telangiectasia].
abstract: Ataxia-telangiectasia (AT) is a severe hereditary autosomal recessive neurodegenerative disease associated with accelerated aging and caused by mutation in both alleles of atm gene. This gene encodes a key protein of cell response to DNA damage--an ATM protein kinase. Normally, upon formation of DNA double strand breaks ATM is autophosphorylated and its active form phospho-ATM (P-ATM) appears. Here we describe a mosaic form of AT in which cells of the same patient with normal atm gene demonstrated the accumulation of P-ATM in response to DNA double-strand breaks-inducing factors whereas in cells bearing a mutant form of atm P-ATM was not detected. The epigenetic markers such as histone deacetylases SIRT1 and SIRT6, and trimethylated forms of histone H3 - H3K9me3 and H3K27me3--were studied in the nuclei of primary fibroblasts derived from patients with different forms of AT and the increase of SIRT6 level was revealed.
authors.forename: M L
authors.initials: ML
authors.lastname: Kuranova
authors.forename: N M
authors.initials: NM
authors.lastname: Pleskach
authors.forename: T A
authors.initials: TA
authors.lastname: Ledashcheva
authors.forename: V M
authors.initials: VM
authors.lastname: Mikhel'son
authors.forename: I M
authors.initials: IM
authors.lastname: Spivak
mesh_terms: D000328:Adult; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D044127:Epigenesis, Genetic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009030:Mosaicism; D010766:Phosphorylation; D061251:Primary Cell Culture; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C447939:SIRT1 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D037761:Sirtuins