GM08505
Fibroblast from Skin, Unspecified
Description:
BLOOM SYNDROME; BLM
RECQ PROTEIN-LIKE 3; RECQL3
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Hereditary Cancers |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
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Biopsy Source
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Unspecified
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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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Simian Virus 40
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Sample Source
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Fibroblast from Skin, Unspecified
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Race
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White
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Ethnicity
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ASHKENAZI
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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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| 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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| 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. |
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| DNA LIGASE I AND II |
Willis et al. (Proc Natl Acad Sci USA 84:8016,1987) reported reduced DNA ligase I and normal DNA ligase II activity in fibroblasts. The DNA ligase I activity is more heat labile than normal. Lehmann et al (Cancer Res 48:6343-6347,1988) observed that this culture showed normal sensitivity to cell killing by dimethyl sulfate at low doses but showed greater sensitivity than normal cells at higher doses. These authors also reported that DNA ligase activity profiles for size fractionated cell-free extracts showed reduced DNA ligase I activity and normal DNA ligase II activity. 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. |
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| MEX PHENOTYPES |
Willis et al. (Proc Natl Acad Sci USA 84:8016,1987) reported a Mex+ phenotype based upon DNA (guanine-O6)-methyltransferase assay. |
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| SISTER CHROMATID EXCHANGE ANALYSIS |
High number of SCEs (60-80 per cell) in transformed fibroblast culture (Willis et al. Proc Natl Acad Sci USA 84:8016-8020,1987). |
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| 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. |
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| Gene |
RECQL3 |
| Chromosomal Location |
15q26.1 |
| Allelic Variant 2 |
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. |
| Remarks |
Clinically affected; short stature; microcephaly; triangular, elongated facies; mild micrognathia; adenocarcinoma of colon; subserous myoma of uterus; hypoplastic, anovulatory ovaries; increased sister chromatid exchange; reduced DNA ligase I activity; near tetraploid line: counts range from 85 to 102 chromosomes per cell; karyotype is abnormal with multiple breaks and rearrangements; 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; this mutation was found in the fibroblast culture from this same donor (AG06040); B.S. Registry #42; SV40 transformed AG06040. |
| Zita Gál, Stavroula Boukoura, Kezia Catharina Oxe, Sara Badawi, Blanca Nieto, Lea Milling Korsholm, Sille Blangstrup Geisler, Ekaterina Dulina, Anna Vestergaard Rasmussen, Christina Dahl, Wei Lv, Huixin Xu, Xiaoguang Pan, Stefanos Arampatzis, Danai-Eleni Stratou, Panagiotis Galanos, Lin Lin, Per Guldberg, Jiri Bartek, Yonglun Luo & Dorthe H. Larsen, Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation Nature Communications: 2024 |
| PubMed ID: 39242676 |
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| Mazouzi A, Moser SC, Abascal F, van den Broek B, Del Castillo Velasco-Herrera M, van der Heijden I, Hekkelman M, Drenth AP, van der Burg E, Kroese LJ, Jalink K, Adams DJ, Jonkers J, Brummelkamp TR, FIRRM/C1orf112 mediates resolution of homologous recombination intermediates in response to DNA interstrand crosslinks Science advances9:eadf4409 2023 |
| PubMed ID: 37256941 |
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| Silveira SC, Buhagiar-Labarchède G, Onclercq-Delic R, Gemble S, Bou Samra E, Mameri H, Duchambon P, Machon C, Guitton J, Amor-Guéret M, A decrease in NAMPT activity impairs basal PARP-1 activity in cytidine deaminase deficient-cells, independently of NAD Scientific reports10:13907 2020 |
| PubMed ID: 32807821 |
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| Subramanian V, Rodemoyer B, Shastri V, Rasmussen LJ, Desler C, Schmidt KH, Bloom syndrome DNA helicase deficiency is associated with oxidative stress and mitochondrial network changes Scientific reports11:2157 2020 |
| PubMed ID: 33495511 |
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| Gratia M, Rodero MP, Conrad C, Bou Samra E, Maurin M, Rice GI, Duffy D, Revy P, Petit F, Dale RC, Crow YJ, Amor-Gueret M, Manel N, Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS The Journal of experimental medicine216:1199-1213 2018 |
| PubMed ID: 30936263 |
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| Behnfeldt JH, Acharya S, Tangeman L, Gocha AS, Keirsey J, Groden J, A tri-serine cluster within the topoisomerase IIa-interaction domain of the BLM helicase is required for regulating chromosome breakage in human cells Human molecular genetics216:1199-1213 2017 |
| PubMed ID: 29385443 |
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| Killen MW, Stults DM, Wilson WA, Pierce AJ, Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes BMC molecular biology13:33 2012 |
| PubMed ID: 23110454 |
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| Popuri V, Ramamoorthy M, Tadokoro T, Singh DK, Karmakar P, Croteau DL, Bohr VA, Recruitment and retention dynamics of RECQL5 at DNA double strand break sites DNA repair11:624-35 2012 |
| PubMed ID: 22633600 |
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| Singh DK, Popuri V, Kulikowicz T, Shevelev I, Ghosh AK, Ramamoorthy M, Rossi ML, Janscak P, Croteau DL, Bohr VA, The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability Nucleic acids research40:6632-48 2012 |
| PubMed ID: 22544709 |
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| Larocque JR, Jasin M, Mechanisms of recombination between diverged sequences in wild-type and BLM-deficient mouse and human cells Molecular and cellular biology30:1887-97 2010 |
| PubMed ID: 20154148 |
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| Bhattacharyya S, Keirsey J, Russell B, Kavecansky J, Lillard-Wetherell K, Tahmaseb K, Turchi JJ, Groden J, Telomerase associated protein 1, HSP90 and topoisomerase IIalpha associate directly with the BLM helicase in immortalized cells using altand modulate its helicase activity using telomeric DNA substrates The Journal of biological chemistry30:1887-97 2009 |
| PubMed ID: 19329795 |
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| Eladad S, Ye TZ, Hu P, Leversha M, Beresten S, Matunis MJ, Ellis NA, Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification Human molecular genetics14:1351-65 2005 |
| PubMed ID: 15829507 |
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| Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W, BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J24(7):1465-76 2005 |
| PubMed ID: 15775963 |
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| Lillard-Wetherell K, Machwe A, Langland GT, Combs KA, Behbehani GK, Schonberg SA, German J, Turchi JJ, Orren DK, Groden J, Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2 Hum Mol Genet13(17):1919-32 2004 |
| PubMed ID: 15229185 |
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| Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM Jr, Stimulation of flap endonuclease-1 by the Bloom's syndrome protein. J Biol Chem279(11):9847-56 2004 |
| PubMed ID: 14688284 |
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| 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 |
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| Jack R. Edelman and Yue J. Lin, Accretion of unstable heterochromatin as the origin of double minute chromosomes: evidence from Bloom Syndrome Cytologia (Tokyo)68:75-82 2003 |
| PubMed ID: 14638871 |
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| Ju R, Muller MT, Histone deacetylase inhibitors activate p21(WAF1) expression via ATM. Cancer Res63(11):2891-7 2003 |
| PubMed ID: 12782595 |
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| Mandola MV, Stoehlmacher J, Muller-Weeks S, Cesarone G, Yu MC, Lenz HJ, Ladner RD, A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res63(11):2898-904 2003 |
| PubMed ID: 12782596 |
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| Traverso G, Bettegowda C, Kraus J, Speicher MR, Kinzler KW, Vogelstein B, Lengauer C, Hyper-recombination and genetic instability in BLM-deficient epithelial cells. Cancer Res63(24):8578-81 2003 |
| PubMed ID: 14695165 |
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| Langland G, Elliott J, Li Y, Creaney J, Dixon K, Groden J, The BLM helicase is necessary for normal DNA double-strand break repair. Cancer Res62(10):2766-70 2002 |
| PubMed ID: 12019152 |
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| 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 |
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| Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies SL, Ryu GH, Freire R, Hickson ID, Jiricny J, Stagljar I., Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1. Nucleic Acids Res29(21):4378-86 2001 |
| PubMed ID: 11691925 |
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| Ouellette MM, McDaniel LD, Wright WE, Shay JW, Schultz RA, The establishment of telomerase-immortalized cell lines representing human
chromosome instability syndromes. Hum Mol Genet9(3):403-11 2000 |
| PubMed ID: 10655550 |
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| Ellis NA, Proytcheva M, Sanz MM, Ye TZ, German J, Transfection of BLM into cultured bloom syndrome cells reduces the sister-chromatid exchange rate toward normal. Am J Hum Genet65(5):1368-74 1999 |
| PubMed ID: 10521302 |
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| Neff NF, Ellis NA, Ye TZ, Noonan J, Huang K, Sanz M, Proytcheva M, The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells. Mol Biol Cell10:665-76 1999 |
| PubMed ID: 10069810 |
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| Prince PR, Ogburn CE, Moser MJ, Emond MJ, Martin GM, Monnat RJ Jr, Cell fusion corrects the 4-nitroquinoline 1-oxide sensitivity of Werner syndrome fibroblast cell lines. Hum Genet105:132-8 1999 |
| PubMed ID: 10480367 |
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| Giesler T, Baker K, Zhang B, McDaniel LD, Schultz RA, Correction of the Bloom syndrome cellular phenotypes. Somat Cell Mol Genet23:303-12 1997 |
| PubMed ID: 9546074 |
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| Tomkinson AE, Starr R, Schultz RA, DNA ligase III is the major high molecular weight DNA joining activity in SV40-transformed human fibroblasts: normal levels of DNA ligase III activity in Bloom syndrome cells. Nucleic Acids Res21:5425-30 1993 |
| PubMed ID: 8265359 |
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| McDaniel LD, Schultz RA, Elevated sister chromatid exchange phenotype of Bloom syndrome cells is
complemented by human chromosome 15. Proc Natl Acad Sci U S A89(17):7968-72 1992 |
| PubMed ID: 1518822 |
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| Sullivan N, Lyne L, Sensitivity of fibroblasts derived from ataxia-telangiectasia patients to calicheamicin gamma 1I. Mutat Res245:171-5 1990 |
| PubMed ID: 1700294 |
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| 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 |
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| 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 |
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| Willis, Structural alterations of DNA ligase I in Bloom syndrome. Proc Natl Acad Sci USA84:8016 (1987):6343-7 1987 |
| PubMed ID: 3180052 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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