GM01492

GM01492 Fibroblast

Description:

BLOOM SYNDROME; BLM
RECQ PROTEIN-LIKE 3; RECQL3

Affected:

Yes

Sex:

Male

Age:

15 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Hereditary Cancers
Chromosome Abnormalities

Class

Repair Defective and Chromosomal Instability Syndromes

Class

Syndromes with Increased Chromosome Breakage

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Ethnicity

ASHKENAZI

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; B.S. Registry #44; increased sister chromatid exchange; chromosome breakage and unstable karyotype; increased post UV irradiation unscheduled DNA synthesis; donor subject is homozygous for a 6-bp deletion/7-bp insertion [6-bp del/7-bp ins] at nucleotide 2,281 of the open reading frame of the RECQL3 gene, which results in a frameshift and a stop codon; donor subject has T>G transversion at the nucleotide preceding the splice acceptor site AG of intron 5 in the p53 gene that results in aberrant splicing of exon 5 and exon 7, omitting exon 6; this mutation generates a transcript that is predicted to encode a truncated p53 protein containing only 189 amino acid residues due to frame shift and a premature stop codon.

Characterizations

Passage Frozen

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

DNASE ACTIVITY

Mezzina et al (Nucleic Acids Res 17:3091-3106,1989) studied DNase activity in this Bloom's syndrome culture. The results presented indicated that the DNase specific activity in crude extracts of this culture was higher than in appropriate control cell cultures.

DNA LIGASE I AND II

Kenne & Ljungquist (Eur J Biochem 174:465-470,1988) reported that this culture shows an increased DNA ligase activity. This activity is 2-3 fold higher than normal human fibroblasts & 5-20 fold higher than 3 other Bloom's syndrome fibroblasts (GM01493, GM02548, & GM03402). The DNA ligase activity in this culture is promoted by a heat-resistant, protease-sensitive factor comigrating with DNA ligases on singlestranded-DNA-cellulose. The factor stimulates DNA ligase I and DNA ligase II, and is not identical to the activity-promoting homologous DNA pairing, which is also enhanced in extracts of this culture. Mezzina et al (Nucleic Acids Res 17:3091-3106,1989) studied DNA ligase activity in this Bloom's syndrome culture. The results presented indicated that the DNA ligase specific activity in crude extracts of this culture was higher than in control cells and that the ligase activity correlated to a major 130 kDa polypeptide.

URACIL DNA GLYCOSYLASE

Seal et al (Proc Natl Acad Sci USA 85:2339-2343,1988) reported that monoclonal antibody, 40.10.09, to normal uracil DNA glycosylase did not react with the uracil DNA glycosylase from this Bloom syndrome culture. Immunoreactivity of the denatured enzyme with antibody 40.10.09 was observed by immunoblot analysis (Vollberg et al, Carcinogenesis 8:1725-1729,1987).

Gene

RECQL3

Chromosomal Location

15q26.1

Allelic Variant 1

604610.0001; BLOOM SYNDROME

Identified Mutation

6-BP DEL/7-BP INS; In 4 ostensibly unrelated persons of Jewish ancestry, Ellis et al. [Cell 83: 655 (1995)] found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. Ellis et al. [Cell 83: 655 (1995)] concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor.

Gene

RECQL3

Chromosomal Location

15q26.1

Allelic Variant 2

604610.0001; BLOOM SYNDROME

Identified Mutation

Phenotypic Data

Remarks

Publications

Mirmohammadsadegh A, Marini A, Nambiar S, Hassan M, Tannapfel A, Ruzicka T, Hengge UR, Epigenetic silencing of the PTEN gene in melanoma Cancer research66:6546-52 2006

PubMed ID: 16818626

Rao VA, Fan AM, Meng L, Doe CF, North PS, Hickson ID, Pommier Y, Phosphorylation of BLM, dissociation from topoisomerase IIIalpha, and colocalization with gamma-H2AX after topoisomerase I-induced replication damage Molecular and cellular biology25:8925-37 2005

PubMed ID: 16199871

Gao H, Chen XB, McGowan CH, Mus81 endonuclease localizes to nucleoli and to regions of DNA damage in human S-phase cells. Mol Biol Cell14(12):4826-34 2003

PubMed ID: 14638871

Trikka D, Fang Z, Renwick A, Jones SH, Chakraborty R, Kimmel M, Nelson DL, Complex SNP-based haplotypes in three human helicases: implications for cancer association studies. Genome Res12(4):627-39 2002

PubMed ID: 11932247

Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA, Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. Hum Mol Genet10(12):1287-98 2001

PubMed ID: 11406610

Magnusson KP, Sandstrom M, Stahlberg M, Larsson M, Flygare J, Hellgren D, Wiman KG, Ljungquist S, p53 splice acceptor site mutation and increased HsRAD51 protein expression in Bloom's syndrome GM1492 fibroblasts. Gene246(1-2):247-54 2000

PubMed ID: 10767546

Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF 3rd, Maul GG, PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol147:221-34 1999

PubMed ID: 10525530

Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, Amor-Gueret M, Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome. Hum Mol Genet6:1427-34 1997

PubMed ID: 9285778

van Laar T, Steegenga WT, Jochemsen AG, Terleth C, van der Eb AJ, GM1492 human diploid skin fibroblasts lack the p53-dependent G1 cell-cycle checkpoint. Biochem Biophys Res Commun217:769-76 1995

PubMed ID: 8554597

van Laar T, Steegenga WT, Jochemsen AG, Terleth C, van der Eb AJ, Bloom's syndrome cells GM1492 lack detectable p53 protein but exhibit normal G1 cell-cycle arrest after UV irradiation. Oncogene9:981-3 1994

PubMed ID: 8108144

Lu X, Lane DP, Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75:765-78 1993

PubMed ID: 8242748

Poot M, Rudiger HW, Hoehn H, Detection of free radical-induced DNA damage with bromodeoxyuridine/Hoechst flow cytometry: implications for Bloom's syndrome. Mutat Res238:203-7 1990

PubMed ID: 1692968

Seal G, Henderson EE, Sirover MA, Immunological alteration of the Bloom's syndrome uracil DNA glycosylase in Epstein-Barr virus-transformed human lymphoblastoid cells. Mutat Res243:241-8 1990

PubMed ID: 2155388

Mezzina M, Nardelli J, Nocentini S, Remault G, Sarasin A, DNA ligase activity in human cell lines from normal donors and Bloom's syndrome patients. Nucleic Acids Res17:3091-106 1989

PubMed ID: 2726453

Nicotera TM, Notaro J, Notaro S, Schumer J, Sandberg AA, Elevated superoxide dismutase in Bloom's syndrome: a genetic condition of oxidative stress. Cancer Res49:5239-43 1989

PubMed ID: 2766291

Vollberg TM, Siegler KM, Cool BL, Sirover MA, Isolation and characterization of the human uracil DNA glycosylase gene. Proc Natl Acad Sci U S A86:8693-7 1989

PubMed ID: 2813420

Kenne K, Ljungquist S, Expression of a DNA-ligase-stimulatory factor in Bloom's syndrome cell line GM1492. Eur J Biochem174:465-70 1988

PubMed ID: 3391163

Lehmann AR, Willis AE, Broughton BC, James MR, Steingrimsdottir H, Harcourt SA, Arlett CF, Lindahl T, Relation between the human fibroblast strain 46BR and cell lines representative of Bloom's syndrome. Cancer Res48:6343-7 1988

PubMed ID: 3180052

Seal G, Brech K, Karp SJ, Cool BL, Sirover MA, Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. Proc Natl Acad Sci U S A85:2339-43 1988

PubMed ID: 3353381

Bubley GJ, Schnipper LE, Effects of Bloom's syndrome fibroblasts on genetic recombination and mutagenesis of herpes simplex virus type 1. Somat Cell Mol Genet13:111-7 1987

PubMed ID: 3031825

Tyrrell RM, Amaudruz F, Evidence for two independent pathways of biologically effective excision repair from its rate and extent in cells cultured from sun-sensitive humans. Cancer Res47:3725-8 1987

PubMed ID: 3109732

Vollberg TM, Seal G, Sirover MA, Monoclonal antibodies detect conformational abnormality of uracil DNA glycosylase in Bloom's syndrome cells. Carcinogenesis8:1725-9 1987

PubMed ID: 3664966

Willis AE, Lindahl T, DNA ligase I deficiency in Bloom's syndrome. Nature325:355-7 1987

PubMed ID: 3808031

Brothman AR, Cram LS, Bartholdi MF, Kraemer PM, Preneoplastic phenotype and chromosome changes of cultured human Bloom syndrome fibroblasts (strain GM 1492). Cancer Res46:791-7 1986

PubMed ID: 3940643

Hurt MM, Moses RE, Conversion of replicative intermediates in human DNA-repair defective cells. Exp Cell Res163:396-404 1986

PubMed ID: 3956584

Kim S, Vollberg TM, Ro JY, Kim M, Sirover MA, O6-methylguanine methyltransferase increases before S phase in normal human cells but does not increase in hypermutable Bloom's syndrome cells. Mutat Res173:141-5 1986

PubMed ID: 3945242

Ockey CH, Saffhill R, Delayed DNA maturation, a possible cause of the elevated sister- chromatid exchange in Bloom's syndrome. Carcinogenesis7:53-7 1986

PubMed ID: 3943145

Hoehn H, Kurnit DM, Intraindividual Y-chromosome heteromorphism [letter] Hum Genet71:278 1985

PubMed ID: 4065902

Gupta PK, Sirover MA, Altered temporal expression of DNA repair in hypermutable Bloom's syndrome cells. Proc Natl Acad Sci U S A81:757-61 1984

PubMed ID: 6583674

Kenne K, Ljungquist S, A DNA-recombinogenic activity in human cells. Nucleic Acids Res12:3057-68 1984

PubMed ID: 6232501

Coohill TP, Moore SP, Grider RA, Action spectra (254-302 nm) for four human photosensitive cell lines. Photochem Photobiol38:105-7 1983

PubMed ID: 6622549

Nicotera, Elevated superoxide dismutase activity in Bloom Syndrome fibroblasts. Am J Hum Genet35:49A (1983):105-7 1983

PubMed ID: 6622549

Shmookler Reis RJ, Goldstein S, Mitochondrial DNA in mortal and immortal human cells. Genome number, integrity, and methylation. J Biol Chem258:9078-85 1983

PubMed ID: 6307991

Taylor MW, Kothari RM, Holland GD, Martinez-Valdez H, Zeige G, A comparison of purine and pyrimidine pools in Bloom's syndrome and normal cells. Cancer Biochem Biophys7:19-25 1983

PubMed ID: 6667451

Giannelli F, Botcherby PK, Avery JA, The effect of aphidicolin on the rate of DNA replication and unscheduled DNA synthesis of Bloom syndrome and normal fibroblasts. Hum Genet60:357-9 1982

PubMed ID: 6809595

Mallick U, Rahmsdorf HJ, Yamamoto N, Ponta H, Wegner RD, Herrlich P, 12-O-tetradecanoylphorbol 13-acetate-inducible proteins are synthesized at an increased rate in Bloom syndrome fibroblasts. Proc Natl Acad Sci U S A79:7886-90 1982

PubMed ID: 6961458

Teo IA, Arlett CF, The response of a variety of human fibroblast cell strains to the lethal effects of alkylating agents. Carcinogenesis3:33-7 1982

PubMed ID: 7067035

Bartram CR, Rudiger HW, Schmidt-Preuss U, Passarge E, Functional deficiency of fibroblasts heterozygous for Bloom syndrome as specific manifestation of the primary defect. Am J Hum Genet33:928-34 1981

PubMed ID: 7325155

Emerit I, Cerutti P, Clastogenic activity from Bloom syndrome fibroblast cultures. Proc Natl Acad Sci U S A78:1868-72 1981

PubMed ID: 6940194

Henson P, Selsky CA, Little JB, Excision of ultraviolet damage and the effect of irradiation on DNA synthesis in a strain of Bloom's syndrome fibroblasts. Cancer Res41:760-6 1981

PubMed ID: 6257383

Hirschi M, Netrawali MS, Remsen JF, Cerutti PA, Formation of DNA single-strand breaks by near-ultraviolet and gamma-rays in normal and Bloom's syndrome skin fibroblasts. Cancer Res41:2003-7 1981

PubMed ID: 7214368

Schmidt-Preuss U, Maack P, Bartram CR, Rudiger HW, Mutagen-induced sister chromatid exchange rate in Bloom syndrome remains unaltered in the presence of Bloom corrective factor. Hum Genet58:432-3 1981

PubMed ID: 6799385

Warren ST, Schultz RA, Chang CC, Wade MH, Trosko JE, Elevated spontaneous mutation rate in Bloom syndrome fibroblasts. Proc Natl Acad Sci U S A78:3133-7 1981

PubMed ID: 6942420

Zbinden I, Cerutti P, Near-ultraviolet sensitivity of skin fibroblasts of patients with Bloom's syndrome. Biochem Biophys Res Commun98:579-87 1981

PubMed ID: 7225114

Alhadeff B, Velivasakis M, Pagan-Charry I, Wright WC, Siniscalco M, High rate of sister chromatid exchanges of Bloom's syndrome chromosomes is corrected in rodent human somatic cell hybrids. Cytogenet Cell Genet27:8-23 1980

PubMed ID: 7389421

Arlett CF, Harcourt SA, Survey of radiosensitivity in a variety of human cell strains. Cancer Res40:926-32 1980

PubMed ID: 7471106

Gupta RS, Goldstein S, Diphtheria toxin resistance in human fibroblast cell strains from normal and cancer-prone individuals. Mutat Res73:331-8 1980

PubMed ID: 7464842

Hohmann P, Species- and cell-specific expression of H1 histones in tissue culture cells. Arch Biochem Biophys205:198-209 1980

PubMed ID: 7447476

Krepinsky AB, Rainbow AJ, Heddle JA, Studies on the ultraviolet light sensitivity of Bloom's syndrome fibroblasts. Mutat Res69:357-68 1980

PubMed ID: 7360151

Remsen JF, Repair of damage by N-acetoxy-2-acetylaminofluorene in Bloom's syndrome. Mutat Res72:151-4 1980

PubMed ID: 7442692

Rudiger HW, Bartram CR, Harder W, Passarge E, Rate of sister chromatid exchanges in Bloom syndrome fibroblasts reduced by co-cultivation with normal fibroblasts. Am J Hum Genet32:150-7 1980

PubMed ID: 7386453

Schonberg S, German J, Sister chromatid exchange in cells metabolically coupled to Bloom's syndrome cells. Nature284:72-4 1980

PubMed ID: 7354874

Tetzner C, Juhl HJ, Rudiger HW, Sister-chromatid exchange induction by metabolically activated retinoids in human diploid fibroblast cultures. Mutat Res79:163-7 1980

PubMed ID: 6933309

Weichselbaum RR, Nove J, Little JB, X-ray sensitivity of fifty-three human diploid fibroblast cell strains from patients with characterized genetic disorders. Cancer Res40:920-5 1980

PubMed ID: 7471105

Cohen MM, Sagi M, Ben-Zur Z, Schaap T, Voss R, Kohn G, Ben-Bassat H, Ataxia telangiectasia: chromosomal stability in continuous lymphoblastoid cell lines. Cytogenet Cell Genet23:44-52 1979

PubMed ID: 761484

German J, Bloom D, Passarge E, Bloom's syndrome. VII. Progress report for 1978. Clin Genet15:361-7 1979

PubMed ID: 436333

Ockey CH, Quantitative replicon analysis of DNA synthesis in cancer-prone conditions and the defects in Bloom's syndrome. J Cell Sci40:125-44 1979

PubMed ID: 536382

Selsky CA, Henson P, Weichselbaum RR, Little JB, Defective reactivation of ultraviolet light-irradiated herpesvirus by a Bloom's syndrome fibroblast strain. Cancer Res39:3392-6 1979

PubMed ID: 225021

Moses RE, Beaudet AL, Apurinic DNA endonuclease activities in repair-deficient human cell lines. Nucleic Acids Res5:463-73 1978

PubMed ID: 634794

Selsky, Defective host-cell reactivation of UV-i rradiated herpes simplex virus by Bloom's syndrome skin fibroblasts. (from DNA Repair Mechanisms, Academic Press, Inc) "DNA Repair Mechanisms"1978, pp 555:463-73 1978

PubMed ID: 634794

German J, Bloom D, Passarge E, Fried K, Goodman RM, Katzenellenbogen I, Laron Z, Legum C, Levin S, Wahrman, Bloom's syndrome. VI. The disorder in Israel and an estimation of the gene frequency in the Ashkenazim. Am J Hum Genet29:553-62 1977

PubMed ID: 930922

Cohen MM, Shaham M, Dagan J, Shmueli E, Kohn G, Cytogenetic investigations in families with ataxia-telangiectasia. Cytogenet Cell Genet15:338-56 1975

PubMed ID: 1222588