Bloom's syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early onset of cancer and for the development of multiple cancers. Loss-of-function mutations of BLM, which codes for a RecQ helicase, cause Bloom's syndrome. The absence of a functional BLM protein causes chromosome instability, excessive homologous recombination, and a greatly increased number of sister chromatid exchanges that are pathognomonic of the syndrome. A common founder mutation designated blmAsh is present in about 1 in 100 persons of Eastern European Jewish ancestry, and there are additional recurrent founder mutations among other populations. Missense, nonsense, and frameshift mutations as well as multiexonic deletions have all been observed. Bloom's syndrome is a prototypical chromosomal instability syndrome, and the somatic mutations that occur as a result of that instability are responsible for the increased cancer risk. Although there is currently no treatment aimed at the underlying genetic abnormality, persons with Bloom's syndrome benefit from sun protection, aggressive treatment of infections, surveillance for insulin resistance, and early identification of cancer.

Journal Section:
Editor's choice
Keywords:
Bloom’s syndrome, <italic>BLM</italic>, Cancer
1.
Adams MD, McVey M, Sekelsky JJ: Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing. Science 299:265-267 (2003).
2.
Antczak A, Kluźniak A, Wokolorczyk, Kashyap A, Jakubowska A, et al: A common nonsense mutation of the BLM gene and prostate cancer risk and survival. Gene 532:173-1766 (2013).
3.
Arora H, Chacon AH, Choudhary S, McLeod MP, Meshkov L, et al: Bloom syndrome. Int J Dermatol 53:798-802 (2014).
4.
Babbe H, Chester N, Leder P, Reizis B: The Bloom's syndrome helicase is critical for development and function of the αβ T-cell lineage. Mol Cell Biol 27:1947-1959 (2007).
5.
Babbe H, McMenamin J, Hobeika E, Wang J, Rodig SJ, et al: Genomic instability resulting from Blm-deficiency compromises development, maintenance, and function of the B cell lineage. J Immunol 182:347-360 (2009).
6.
Bachrati CZ, Borts RH, Hickson ID: Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase. Nucleic Acids Res 34:2269-2279 (2006).
7.
Baris HN, Kedar I, Halpern GJ, Shohat T, Magal N, et al: Prevalence of breast and colorectal cancer in Ashkenazi Jewish carriers of Fanconi anemia and Bloom syndrome. Isr Med Assoc J 9:847-850 (2007).
8.
Beamish H, Kedar P, Kaneko H, Chen P, Fukao T, et al: Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM. J Biol Chem 277:30515-30523 (2002).
9.
Bhisitkul RB, Rizen M: Bloom syndrome: multiple retinopathies in a chromosome breakage disorder. Br J Ophthalmol 88:354-357 (2004).
10.
Bischof O, Kim SH, Irving J, Beresten S, Ellis NA, Campisi J: Regulation and localization of the Bloom syndrome protein in response to DNA damage. J Cell Biol 153:367-380 (2001).
11.
Bloom D: Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs. AMA Am J Dis Child 88:754-758 (1954).
12.
Bogdanova N, Togo AV, Ratajska M, Kluźniak W, Takhirova Z, et al: Prevalence of the BLM nonsense mutation, p.Q548X in ovarian cancer patients from Central and Eastern Europe. Fam Cancer 14:145-149 (2015).
13.
Brock PR, de Zegher F, Casteels-Van Daele M, Vanderschueren-Lodeweyckx M: Malignant disease in Bloom's syndrome children treated with growth hormone. Lancet 337:1345-1346 (1991).
14.
Cefle K, Ozturk S, Gozum N, Duman N, Mantar F, et al: Lens opacities in Bloom syndrome: case report and review of the literature. Ophthalmic Genet 28:175-178 (2007).
15.
Chaganti RSK, Schonberg S, German J: A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. Proc Nat Acad Sci USA 71:4508-4512 (1974).
16.
Chan KL, North PS, Hickson ID: BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. EMBO J 26:3397-3409 (2007).
17.
Chan KL, Palmai-Pallag T, Ying S, Hickson ID: Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat Cell Biol 11:753-760 (2009).
18.
Chen CF, Brill SJ: An essential DNA strand-exchange activity is conserved in the divergent N-termini of BLM orthologs. EMBO J 29:1713-1725 (2010).
19.
Cheok CF, Wu L, Garcia PL, Janscak P, Hickson ID: The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA. Nucleic Acids Res 33:3932-3941 (2005).
20.
Chester N, Kuo F, Kozak C, O'Hara CD, Leder P: Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene. Genes Dev 12:3382-3393 (1998).
21.
Chisolm CA, Bray MJ, Karns LB: Successful pregnancy in a woman with Bloom syndrome. Am J Med Genet 102:136-138 (2001).
22.
Cleary SP, Zhang W, Di Nicola N, Aronson M, Aube J, et al: Heterozygosity for the BLMAsh mutation and cancer risk. Cancer Res 63:1769-1771 (2003).
23.
Croteau DL, Popuri V, Opresko PL, Bohr VA: Human RecQ helicases in DNA repair, recombination, and replication. Annu Rev Biochem 83:519-552 (2014).
24.
Davies SL, North PS, Dart A, Lakin ND, Hickson ID: Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest. Mol Cell Biol 24:1279-1291 (2004).
25.
de Voer RM, Hanh MM, Mensenkamp AR, Hoischen A, Gilissen C, et al: Deleterious germline BLM mutations and the risk for early-onset colorectal cancer. Sci Rep 5:14060 (2015).
26.
Diaz A, Vogiatzi MG, Sanz MM, German J: Evaluation of short stature, carbohydrate metabolism and other endocrinopathies in Bloom's syndrome. Horm Res 66:111-117 (2006).
27.
Dou H, Huang C, Singh M, Carpenter PB, Yeh ET: Regulation of DNA repair through deSUMOylation and SUMOylation of replication protein A complex. Mol Cell 39:333-345 (2010).
28.
Draznin M, Robles DT, Nguyen V, Berg D: An unusual case of Bloom syndrome presenting with basal cell carcinoma. Dermatol Surg 35:131-134 (2009).
29.
Drosopoulos WC, Kosiyatrakul ST, Schildkraut CL: BLM helicase facilitates telomere replication during leading strand synthesis of telomeres. J Cell Biol 210:191-208 (2015).
30.
Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, et al: SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation. J Cell Sci 112:381-393 (1999).
31.
Dutertre S, Ababou M, Onclercq R, Delic J, Chatton B, et al: Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase. Oncogene 19:2731-2738 (2000).
32.
Eladad S, Ye TZ, Hu P, Leversha M, Beresten S, et al: Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification. Hum Mol Genet 14:1351-1365 (2005).
33.
Ellis NA, Roe AM, Kozloski J, Proytcheva M, Falk C, German J: Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome. Am J Hum Genet 55:453-460 (1994).
34.
Ellis NA, Lennon DJ, Proytcheva M, Alhadeff B, Henderson EE, German J: Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of Bloom syndrome cells. Am J Hum Genet 57:1019-1027 (1995a).
35.
Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, et al: The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83:655-666 (1995b).
36.
Ellis NA, Ciocci S, Proytcheva M, Lennon D, Groden J, et al: The Ashkenazic Jewish Bloom syndrome mutation blmAsh is present in non-Jewish Americans of Spanish ancestry. Am J Hum Genet 63:1685-1693 (1998).
37.
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 Genet 65:1368-1374 (1999).
38.
Ellis NA, Ciocci S, German J: Back mutation can produce phenotype reversion in Bloom syndrome somatic cells. Hum Genet 108:167-173 (2001).
39.
Etzioni A, Lahat N, Benderly A, Katz R, Pollack S: Humoral and cellular immune dysfunction in a patient with Bloom's syndrome and recurrent infections. J Clin Lab Immunol 28:151-154 (1989).
40.
Evans HJ, Adams AC, Clarkson JM, German J: Chromosome aberrations and unscheduled DNA synthesis in X- and UV-irradiated lymphocytes from a boy with Bloom's syndrome and a man with xeroderma pigmentosum. Cytogenet Cell Genet 20:124-140 (1978).
41.
German J: Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients. Am J Hum Genet 21:196-227 (1969).
42.
German J: Bloom's syndrome. XX. The first 100 cancers. Cancer Genet Cytogenet 93:100-106 (1997).
43.
German J, Archibald R, Bloom D: Chromosomal breakage in a rare and probably genetically determined syndrome of man. Science 148:506-507 (1965).
44.
German J, Crippa LP, Bloom D: Bloom's syndrome. III. Analysis of the chromosome aberration characteristic of this disorder. Chromosoma 48:361-366 (1974).
45.
German J, Bloom D, Passarge E, Fried K, Goodman RM, et al: Bloom's syndrome. VI. The disorder in Israel and an estimation of the gene frequency in the Ashkenazim. Am J Hum Genet 29:553-562 (1977a).
46.
German J, Schonberg S, Louie E, Chaganti RSK: Bloom's syndrome. IV. Sister chromatid exchanges in lymphocytes. Am J Hum Genet 29:248-255 (1977b).
47.
German J, Roe AM, Leppert MF, Ellis NA: Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. Proc Natl Acad Sci USA 91:6669-6673 (1994).
48.
German J, Ellis NA, Proytcheva M: Bloom's syndrome. XIX. Cytogenetic and population evidence for genetic heterogeneity. Clin Genet 49:223-231 (1996).
49.
German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA: Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. Hum Mut 28:743-753 (2007).
50.
Gibbons B, Scott D, Hungerford JL, Cheung KL, Harrison C, et al: Retinoblastoma in association with the chromosome breakage syndromes Fanconiʼs anaemia and Bloom's syndrome: clinical and cytogenetic findings. Clin Genet 47:311-317 (1995).
51.
Goss KH, Risinger MA, Kordich JJ, Sanz MM, Straughen JE, et al: Enhanced tumor formation in mice heterozygous for Blm mutation. Science 297:2051-2053 (2002).
52.
Grabowski MM, Svrzikapa N, Tissenbaum HA: Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans. Mech Ageing Dev 126:1314-1321 (2005).
53.
Gretzula JC, Hevia O, Weber PJ: Bloom's syndrome. J Am Acad Dermatol 17:479-488 (1987).
54.
Grierson PM, Lillard K, Behbehani GK, Combs KA, Bhattacharyya S, et al: BLM helicase facilitates RNA polymerase I-mediated ribosomal RNA transcription. Hum Mol Genet 21:1172-1183 (2012).
55.
Grierson PM, Acharya S, Groden J: Collaborating functions of BLM and DNA topoisomerase I in regulating human rDNA transcription. Mutat Res 743-744:89-96 (2013).
56.
Gruber SB, Ellis NA, Scott KK, Almog R, Kolachana P, et al: BLM heterozygosity and the risk of colorectal cancer. Science 297:2013 (2002).
57.
Hand R, German J: A retarded rate of DNA chain growth in Bloomʼs syndrome. Proc Natl Acad Sci USA 72:758-762 (1975).
58.
Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, et al: Evidence for BLM and topoisomerase IIIα interaction in genomic stability. Hum Mol Genet 10:1287-1298 (2001).
59.
Hütteroth TH, Litwin SD, German J: Abnormal immune responses of Bloom's syndrome lymphocytes in vitro. J Clin Invest 56:1-7 (1975).
60.
Jian-Bing W, Cheng-Rang L, Yi-Ping M, Sheng N, Hui L, Lin L: A case of Bloom syndrome with uncommon clinical manifestations confirmed on genetic testing. Cutis 97:E10-13 (2016).
61.
Johnson FB, Lombard DB, Neff NF, Mastrangelo MA, Dewolf W, et al: Association of the Bloom syndrome protein with topoisomerase IIIα in somatic and meiotic cells. Cancer Res 60:1162-1167 (2000).
62.
Johnson JE, Cao K, Ryvkin P, Wang LS, Johnson FB: Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential. Nucleic Acids Res 38:1114-1122 (2010).
63.
Kaneko H, Kondo N: Clinical features of Bloom syndrome and function of the causative gene, BLM helicase. Expert Rev Mol Diagn 4:393-401 (2004).
64.
Karow JK, Chakraverty RK, Hickson ID: The Bloom's syndrome gene product is a 3′-5′ DNA helicase. J Biol Chem 272:30611-30614 (1997).
65.
Kauli R, Prager-Iewin R, Kaufman H, Laron Z: Gonadal function in Bloom's syndrome. Clin Endocrinol (Oxf) 6:285-289 (1977).
66.
Kawabe T, Tsuyama N, Kitao S, Nishikawa K, Shimamoto A, et al: Differential regulation of human RecQ family helicases in cell transformation and cell cycle. Oncogene 19:4764-4772 (2000).
67.
Keller C, Keller KR, Shew SB, Plon SE: Growth deficiency and malnutrition in Bloom syndrome. J Pediatr 134:472-479 (1999).
68.
Kim SY, Hakoshima T, Kitano K: Structure of the RecQ C-terminal domain of human Bloom syndrome protein. Sci Rep 3:3294 (2013).
69.
Kim YM, Yang I, Lee J, Koo HS: Deficiency of Bloom's syndrome protein causes hypersensitivity of C. elegans to ionizing radiation but not to UV radiation, and induces p53-dependent physiological apoptosis. Mol Cells 20:228-234 (2005).
70.
Kitano K: Structural mechanisms of human RecQ helicases WRN and BLM. Front Genet 5:366 (2014).
71.
Kitano K, Yoshihara N, Hakoshima T: Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. J Biol Chem 282:2717-2728 (2007).
72.
Kitano K, Kim SY, Hakoshima T: Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN. Structure 18:177-187 (2010).
73.
Kondo N, Motoyoshi F, Mori S, Kuwabara N, Orii T, German J: Long-term study of the immunodeficiency of Bloom's syndrome. Acta Paediatr 81:86-90 (1992).
74.
Kusano K, Johnson-Schlitz DM, Engels WR: Sterility of Drosophila with mutations in the Bloom syndrome gene - complementation by Ku70. Science 291:2600-2602 (2001).
75.
Laitman Y, Boker-Keinan L, Berkenstadt M, Liphsitz I, Weissglas-Volkov D, et al: The risk for developing cancer in Israeli ATM, BLM, and FANCC heterozygous mutation carriers. Cancer Genet 209:70-74 (2016).
76.
Lallemand-Breitenbach V, de Thé H: PML nuclear bodies. Cold Spring Harb Perspect Biol 2:a000661 (2010).
77.
Larsen NB, Hickson ID: RecQ helicases: conserved guardians of genomic integrity. Adv Exp Med Biol 767:161-184 (2013).
78.
Li L, Eng C, Desnick RJ, German J, Ellis NA: Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish population. Mol Genet Metab 64:286-290 (1998).
79.
Lopez-Contreras AJ, Ruppen I, Nieto-Soler M, Murga M, Rodriguez-Acebes S, et al: A proteomic characterization of factors enriched at nascent DNA molecules. Cell Rep 3:1105-1116 (2013).
80.
Luo G, Santoro IM, McDaniel LD, Nishijima I, Mills M, et al: Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nat Genet 26:424-429 (2000).
81.
Machwe A, Xiao L, Groden J, Matson SW, Orren DK: RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange. J Biol Chem 280:23397-23407 (2005).
82.
Maizels N, Gray LT: The G4 genome. PLoS Genet 9:e1003468 (2013).
83.
Masmoudi A, Marrakchi S, Kamoun H, Chaaben H, Ben Salah G, et al: Clinical and laboratory findings in 8 patients with Bloom's syndrome. J Dermatol Case Rep 6:29-33 (2012).
84.
Matunis MJ, Zhang XD, Ellis NA: SUMO: the glue that binds. Dev Cell 11:596-597 (2006).
85.
McDaniel LD, Schultz RA: Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15. Proc Natl Acad Sci USA 89:7968-7972 (1992).
86.
McDaniel LD, Chester N, Watson M, Borowsky AD, Leder P, Schultz RA: Chromosome instability and tumor predisposition inversely correlate with BLM protein levels. DNA Repair (Amst) 2:1387-1404 (2003).
87.
McGowan J, Maize J, Cook J: Lupus-like histopathology in Bloom syndrome: reexamining the clinical and histologic implications of photosensitivity. Am J Dermatopathol 31:786-791 (2009).
88.
McVey M, Andersen SL, Broze Y, Sekelsky J: Multiple functions of Drosophila BLM helicase in maintenance of genome stability. Genetics 176:1979-1992 (2007).
89.
Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, et al: A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol Cell Biol 23:3417-3426 (2003).
90.
Mohaghegh P, Karow JK, Brosh RM Jr, Bohr VA, Hickson ID: The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res 29:2843-2849 (2001).
91.
Mulcahy MT, French M: Pregnancy in Bloom's syndrome. Clin Genet 19:156-158 (1981).
92.
Nair G, Lobo I, Jayalaksmi TK, Uppe A, Jindal S, et al: Bloom syndrome with lung involvement. Lung India 26:92-92 (2009).
93.
Neff NF, Ellis NA, Ye TZ, Noonan J, Huang K, et al: The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells. Mol Biol Cell 10:665-676 (1999).
94.
Nguyen GH, Tang W, Robles AI, Beyer RP, Gray LT, et al: Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs. Proc Natl Acad Sci USA 111:9905-9910 (2014).
95.
Ouyang KJ, Woo LL, Zhu J, Huo D, Matunis MJ, Ellis NA: SUMO modification regulates BLM and RAD51 interaction at damaged replication forks. PLoS Biol 7:e1000252 (2009).
96.
Ouyang KJ, Yagle MK, Matunis MJ, Ellis NA: BLM SUMOylation regulates ssDNA accumulation at stalled replication forks. Front Genet 4:167 (2013).
97.
Ozawa T, Kondo N, Motoyoshi F, Kasahara K, Oril T: DNA mutation induced in the sequence upstream of the secreted MY C-terminal coding sequence by ultraviolet irradiation in the cell line of Bloom's syndrome. Eur J Immunogenet 22:163-169 (1995).
98.
Popuri V, Bachrati CZ, Muzzolini L, Mosedale G, Costantini S, et al: The Human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities. J Biol Chem 283:17766-17776 (2008).
99.
Prokofyeva D, Bogdanova N, Dubrowinskaja N, Bermisheva M, Takhirova Z, et al: Nonsense mutation p.Q548X in BLM, the gene mutated in Bloom's syndrome, is associated with breast cancer in Slavic populations. Breast Cancer Res Treat 137:533-539 (2013).
100.
Rao VA, Fan AM, Meng L, Doe CF, North PS, et al: Phosphorylation of BLM, dissociation from topoisomerase IIIα, and colocalization with γ-H2AX after topoisomerase I-induced replication damage. Mol Cell Biol 25:8925-8937 (2005).
101.
Relhan V, Sinhan S, Bhatnagar T, Garg VK, Kochhar A: Bloom syndrome with extensive pulmonary involvement in a child. Indian J Dermatol 60:217 (2015).
102.
Renes JS, Willemsen RH, Wagner A, Finken MJJ, Hokken-Koelega ACS: Bloom syndrome in short children born small for gestational age: a challenging diagnosis. J Clin Endocrinol Metab 98:3932-3938 (2013).
103.
Rhodes D, Lipps HJ: G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res 43:8627-8637 (2015).
104.
Risch N, Tang H, Katzenstein H, Ekstein J: Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection. Am J Hum Genet 72:812-822 (2003).
105.
Roa BB, Savino CV, Richards CS: Ashkenazi Jewish population frequency of the Bloom syndrome gene 2281Δ6ins7 mutation. Genet Test 3:219-221 (1999).
106.
Sahn EE, Husset RH 3rd, Christmann LM: A case of Bloom syndrome with conjunctival telangiectasia. Pediatr Dermatol 14:120-124 (1997).
107.
Sanz MM, Ellis NA, German J: Cellular localization of nonfunctional BLM protein in cells from persons with Bloom's syndrome (BS) who have inherited missense mutations (abstract 425). Abstracts 50th Annu Meet Am Soc Hum Genet, Philadelphia, October 2000. Am J Hum Genet 67 4 Suppl 2:9-478 (2000a).
108.
Sanz MM, Proytcheva M, Ellis NA, Holloman WK, German J: BLM, the Bloom's syndrome protein, varies during the cell cycle in its amount, distribution, and co-localization with other nuclear proteins. Cytogenet Cell Genet 91:217-223 (2000b).
109.
Sanz MM, German J, Cunniff C: Bloom's Syndrome, in Pagon RA, Adam MP, Ardinger HH, et al (eds): GeneReviews® [Internet]. (University of Washington, Seattle 1993-2016). Initial posting: 2006 Mar 22; last update: 2016 Apr 7.
110.
Sato A, Mishima M, Nagai A, Kim SY, Ito Y, et al: Solution structure of the HRDC domain of human Bloom syndrome protein BLM. J Biochem 148:517-525 (2010).
111.
Shahrabani-Gargir L, Shomrat R, Yaron Y, Orr-Urtreger A, Groden J, Legum C: High frequency of a common Bloom syndrome Ashkenazi mutation among Jews of Polish origin. Genet Test 2:293-296 (1998).
112.
Sirbu BM, Couch FB, Feigerle JT, Bhaskara S, Hiebert SW, Cortez D: Analysis of protein dynamics at active, stalled, and collapsed replication forks. Genes Dev 25:1320-1327 (2011).
113.
Sokolenko AP, Iyevleva AG, Preobrazhenskaya EV, Mitiushkina NV, Abysheva SN, et al: High prevalence and breast cancer predisposing role of the BLM c.1642C>T (Q548X) mutation in Russia. Int J Cancer 130:2867-2873 (2012).
114.
Stahnke N: Leukemia in growth-hormone-treated patients: an update, 1992. Horm Res 38 Suppl 1:56-62 (1992).
115.
Sun H, Karow JK, Hickson ID, Maizels N: The Bloom's syndrome helicase unwinds G4 DNA. J Biol Chem 273:27587-27592 (1998).
116.
Swan MK, Legris V, Tanner A, Reaper PM, Vial S, et al: Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA. Acta Crystallogr D Biol Crystallogr 70:1465-1475 (2014).
117.
Taniguchi N, Mukai M, Nagaoki T, Miyawaki T, Moriya N, et al: Impaired B-cell differentiation and T-cell regulatory function in four patients with Bloom's syndrome. Clin Immunol Immunopath 22:247-258 (1982).
118.
Tereshchenko IV, Chen Y, McDaniel LD, Schultz RA, Tischfield JA, Shao C: Small scale genetic alterations contribute to increased mutability at the X-linked Hprt locus in vivo in Blm hypomorphic mice. DNA Repair (Amst) 9:551-557 (2010).
119.
Thompson ER, Doyle MA, Ryland GL, Rowley SM, Choong DY, et al: Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet 8:e1002894 (2012).
120.
Turley H, Wu L, Canamero M, Gatter KC, Hickson ID: The distribution and expression of the Bloom's syndrome gene product in normal and neoplastic human cells. Br J Cancer 85:261-265 (2001).
121.
van Brabant AJ, Ye T, Sanz M, German III JL, Ellis NA, Holloman WK: Binding and melting of D-loops by the Bloom syndrome helicase. Biochemistry 39:14617-14625 (2000).
122.
Van Kerckhove CW, Ceuppens JL, Vanderschueren-Lodeweyckx M, Eggermont E, Vertessen S, Stevens EA: Bloom's syndrome. Clinical features and immunologic abnormalities of four patients. Am J Dis Child 142:1089-1093 (1988).
123.
Wang Q, Lv H, Lv W, Shi M, Zhang M, et al: Genome-wide haplotype association study identifies BLM as a risk gene for prostate cancer in Chinese population. Tumor Biol 36:2703-2707 (2015).
124.
Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, et al: Functional interaction of p53 and BLM DNA helicase in apoptosis. J Biol Chem 276:32948-32955 (2001).
125.
Weemaes CMR, Bakkeren AJM, ter Haar BGA, Hustinx TWJ, van Munster PJJ: Immune responses in four patients with Bloom syndrome. Clin Immunol Immunopathol 12:12-19 (1979).
126.
Weksberg R, Smith C, Anson-Cartwright L, Maloney K: Bloom syndrome: a single complementation group defines patients of diverse ethnic origin. Am J Hum Genet 42:816-824 (1988).
127.
Wicky C, Alpi A, Passannante M, Rose A, Gartner A, Müller F: Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line. Mol Cell Biol 24:5016-5027 (2004).
128.
Wu L, Hickson ID: The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIα. Nucleic Acids Res 30:4823-4829 (2002).
129.
Wu L, Hickson ID: The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426:870-874 (2003).
130.
Wu L, Chan KL, Ralf C, Bernstein DA, Garcia PL, et al: The HRDC domain of BLM is required for the dissolution of double Holliday junctions. EMBO J 24:2679-2687 (2005).
131.
Wu L, Davies SL, Levitt NC, Hickson ID: Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J Biol Chem 276:19375-19381 (2001).
132.
Wu Y: Unwinding and rewinding: double faces of helicase? J Nucleic Acids 2012:140601 (2012).
133.
Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, et al: BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J 24:1465-1476 (2005).
134.
Zauber NP, Sabbath-Solitare M, Marotta S, Zauber AG, Foulkes W, et al: Clinical and genetic findings in an Ashkenazi Jewish population with colorectal neoplasms. Cancer 104:719-729 (2005).
135.
Zhong S, Hu P, Ye TZ, Stan R, Ellis NA, Pandolfi PP: A role for PML and the nuclear body in genomic stability. Oncogene 18:7941-7947 (1999).
136.
Zhu J, Zhu S, Guzzo CM, Ellis NA, Sung KS, et al: Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification. J Biol Chem 283:29405-29415 (2008).
© 2016 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2016
You do not currently have access to this content.