NG00780
DNA from Fibroblast
Description:
WERNER SYNDROME; WRN REPLICATION FOCUS-FORMING ACTIVITY 1, INCLUDED; FFA1, INCLUDED
RECQ PROTEIN-LIKE 2; RECQL2
NIA AGING CELL REPOSITORY DNA PANEL - AGING SYNDROMES
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Repository
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NIA Aging Cell Culture Repository
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| Subcollection |
Heritable Diseases |
| Quantity |
10ug |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Skin
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
5.11 |
| Passage Frozen |
5 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| Gene |
RECQL2 |
| Chromosomal Location |
8p12-p11.2 |
| Allelic Variant 1 |
604611.0006; WERNER SYNDROME |
| Identified Mutation |
ARG368TER; In 1 Caucasian and 3 Japanese patients with Werner syndrome (277700), Oshima et al. [Hum. Molec. Genet. 5: 1909-1913 (1996)] first reported this mutation (1336C-T), located in exon 9 of the WRN gene, that was predicted to produce a truncated protein lacking WRN helicase function. |
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| Gene |
RECQL2 |
| Chromosomal Location |
8p12-p11.2 |
| Allelic Variant 2 |
604611.0006; WERNER SYNDROME |
| Identified Mutation |
ARG368TER; In 1 Caucasian and 3 Japanese patients with Werner syndrome (277700), Oshima et al. [Hum. Molec. Genet. 5: 1909-1913 (1996)] first reported this mutation (1336C-T), located in exon 9 of the WRN gene, that was predicted to produce a truncated protein lacking WRN helicase function. |
| Remarks |
The donor's parents are second cousins. The donor had features of sclerodactyly (onset at age 24), marked bowing of legs, bilateral cataracts, premature graying of the hair, hypogonadism, impotence, progressive degenerative joint disease, high-pitched voice, and progressive peripheral insufficiency and cutaneous ulcers resulting in lumbar sympathectomy. Donor died at age 63 due to gastrointestinal tract hemorrhage, peritonitis, and acute respiratory distress. The biopsy was taken ante-mortem on 4/4/80. The culture was initiated using explants of minced skin tissue. The cell morphology is fibroblast-like. The culture is a mosaic with karyotype: 46,XY/46,XY,inv(5)(q11.2q22)/46,XY,inv(5)(q11.2q22),t(8;16)(q24.1;q24), t(9;15)(p13;q15),inv(11)(q21q23); 24%/22%/10% with 44% of cells examined showing other chromosomal abnormalities. The donor subject is homozygous for a C>T transition at nucleotide 1336 in exon 9 of the RECQL2 gene (1336C>T) resulting in an amino acid change at codon 368 from arginine to a stop codon [Arg368Ter (R368X)]. The legacy karyotype description shown in this Remark may not be representative of the current available product. |
| Della Valle F, Reddy P, Yamamoto M, Liu P, Saera-Vila A, Bensaddek D, Zhang H, Prieto Martinez J, Abassi L, Celii M, Ocampo A, Nuñez Delicado E, Mangiavacchi A, Aiese Cigliano R, Rodriguez Esteban C, Horvath S, Izpisua Belmonte JC, Orlando V, LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes Science translational medicine14:eabl6057 2022 |
| PubMed ID: 35947677 |
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| Tu J, Wan C, Zhang F, Cao L, Law PWN, Tian Y, Lu G, Rennert OM, Chan WY, Cheung HH, Genetic correction of Werner syndrome gene reveals impaired pro-angiogenic function and HGF insufficiency in mesenchymal stem cells Aging cell14:e13116 2019 |
| PubMed ID: 32320127 |
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| Wang S, Liu Z, Ye Y, Li B, Liu T, Zhang W, Liu GH, Zhang YA, Qu J, Xu D, Chen Z, Ectopic hTERT expression facilitates reprograming of fibroblasts derived from patients with Werner syndrome as a WS cellular model Cell death & disease9:923 2017 |
| PubMed ID: 30206203 |
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| Li B, Jog SP, Reddy S, Comai L, WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-mediated telomere shortening Molecular and cellular biology28:1892-904 2008 |
| PubMed ID: 18212065 |
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| Marciniak RA, Cavazos D, Montellano R, Chen Q, Guarente L, Johnson FB, A novel telomere structure in a human alternative lengthening of telomeres cell line. Cancer Res65(7):2730-7 2005 |
| PubMed ID: 15805272 |
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| Baird DM, Davis T, Rowson J, Jones CJ, Kipling D, Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells. Hum Mol Genet13(14):1515-24 2004 |
| PubMed ID: 15150162 |
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| Taylor TJ, Knipe DM, Proteomics of herpes simplex virus replication compartments: association of cellular DNA replication, repair, recombination, and chromatin remodeling proteins with ICP8 J Virol78(11):5856-66 2004 |
| PubMed ID: 15140983 |
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| Grandori C, Wu KJ, Fernandez P, Ngouenet C, Grim J, Clurman BE, Moser MJ, Oshima J, Russell DW, Swisshelm K, Frank S, Amati B, Dalla-Favera R, Monnat RJ Jr., Werner syndrome protein limits MYC-induced cellular senescence. Genes Dev17(13):1569-74 2003 |
| PubMed ID: 12842909 |
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| von Kobbe C, Harrigan JA, May A, Opresko PL, Dawut L, Cheng WH, Bohr VA, Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage. Mol Cell Biol23(23):8601-13 2003 |
| PubMed ID: 14612404 |
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| Blander G, Zalle N, Daniely Y, Taplick J, Gray MD, Oren M, DNA damage-induced translocation of the Werner helicase is regulated by
acetylation. J Biol Chem277(52):50934-40 2002 |
| PubMed ID: 12384494 |
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| Choi D, Whittier PS, Oshima J, Funk WD, Telomerase expression prevents replicative senescence but does not fully reset mRNA expression patterns in Werner syndrome cell strains. FASEB J15(6):1014-20 2001 |
| PubMed ID: 11292662 |
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| Pichierri P, Franchitto A, Mosesso P, Palitti F, Werner's syndrome protein is required for correct recovery after replication arrest and DNA damage induced in S-phase of cell cycle. Mol Biol Cell12(8):2412-21 2001 |
| PubMed ID: 11514625 |
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| Blander G, Zalle N, Leal JF, Bar-Or RL, Yu CE, Oren M, The Werner syndrome protein contributes to induction of p53 by DNA damage. FASEB J14(14):2138-40 2000 |
| PubMed ID: 11023999 |
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| Machwe A, Orren DK, Bohr VA, Accelerated methylation of ribosomal RNA genes during the cellular senescence of
Werner syndrome fibroblasts. FASEB J14(12):1715-24 2000 |
| PubMed ID: 10973920 |
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| Spillare EA, Robles AI, Wang XW, Shen JC, Yu CE, Schellenberg GD, Harris CC, p53-mediated apoptosis is attenuated in Werner syndrome cells. Genes Dev13:1355-60 1999 |
| PubMed ID: 10364153 |
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| Marciniak RA, Lombard DB, Johnson FB, Guarente L, Nucleolar localization of the Werner syndrome protein in human cells. Proc Natl Acad Sci U S A95(12):6887-92 1998 |
| PubMed ID: 9618508 |
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| Yu CE, Oshima J, Wijsman EM, Nakura J, Miki T, Piussan C, Matthews S, Fu YH,
Mulligan J, Martin GM, Schellenberg GD, Mutations in the consensus helicase domains of the Werner syndrome gene.
Werner's Syndrome Collaborative Group. Am J Hum Genet60(2):330-41 1997 |
| PubMed ID: 9012406 |
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| Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al, A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A92:9363-7 1995 |
| PubMed ID: 7568133 |
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| Saito H, Moses RE, Immortalization of Werner syndrome and progeria fibroblasts Experimental cell research192:373-9 1991 |
| PubMed ID: 1671011 |
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| Winkles JA, O'Connor ML, Friesel R, Altered regulation of platelet-derived growth factor A-chain and c-fos gene expression in senescent progeria fibroblasts. J Cell Physiol144:313-25 1990 |
| PubMed ID: 2166059 |
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| Bauer EA, Uitto J, Tan EM, Holbrook KA, Werner's syndrome. Evidence for preferential regional expression of a generalized mesenchymal cell defect. Arch Dermatol124:90-101 1988 |
| PubMed ID: 3337548 |
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| Cowles EA, Brauker JH, Anderson RL, Turnover of sulfated glycosaminoglycans in fibroblasts derived from patients with Werner's syndrome. Exp Cell Res168:347-57 1987 |
| PubMed ID: 3100317 |
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| Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER, Age-related changes in oxidized proteins. J Biol Chem262:5488-91 1987 |
| PubMed ID: 3571220 |
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| Bauer EA, Silverman N, Busiek DF, Kronberger A, Deuel TF, Diminished response of Werner's syndrome fibroblasts to growth factors PDGF and FGF. Science234:1240-3 1986 |
| PubMed ID: 3022382 |
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| Chapman ML, Zaun MR, Gracy RW, Changes in NAD levels in human lymphocytes and fibroblasts during aging and in premature aging syndromes. Mech Ageing Dev21:157-67 1983 |
| PubMed ID: 6223188 |
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| Puvion-Dutilleul F, Macieira-Coelho A, Aging dependent nucleolar and chromatin changes in cultivated fibroblasts. Cell Biol Int Rep7:61-71 1983 |
| PubMed ID: 6831570 |
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| Tollefsbol TO, Zaun MR, Gracy RW, Increased lability of triosephosphate isomerase in progeria and Werner's syndrome fibroblasts. Mech Ageing Dev20:93-101 1982 |
| PubMed ID: 7176709 |
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