bloom syndrome


Summary: An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.

Top Publications

  1. German J, Roe A, Leppert M, Ellis N. Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. Proc Natl Acad Sci U S A. 1994;91:6669-73 pubmed
    ..In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene ..
  2. Mirzaei H, Schmidt K. Non-Bloom syndrome-associated partial and total loss-of-function variants of BLM helicase. Proc Natl Acad Sci U S A. 2012;109:19357-62 pubmed publisher
    b>Bloom syndrome (BS) is an autosomal recessive disorder caused by mutations in the RecQ-like DNA helicase BLM, which functions in the maintenance of genome stability...
  3. Amor Gueret M. Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis. Cancer Lett. 2006;236:1-12 pubmed
    b>Bloom syndrome (BS) displays one of the strongest known correlations between chromosomal instability and an increased risk of malignancy at an early age...
  4. Lindor N, Furuichi Y, Kitao S, Shimamoto A, Arndt C, Jalal S. Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome. Am J Med Genet. 2000;90:223-8 pubmed
    ..Two other recessive disorders, Bloom syndrome and Werner syndrome, are known to be due to other human RECQ helicase gene mutations...
  5. Thompson L, Schild D. Recombinational DNA repair and human disease. Mutat Res. 2002;509:49-78 pubmed
    ..b>Bloom syndrome involves a defect in the BLM helicase, which seems to play a role in restarting DNA replication forks that are ..
  6. Bergeron K, Murphy E, Brown L, Almeida K. Critical interaction domains between bloom syndrome protein and RAD51. Protein J. 2011;30:1-8 pubmed publisher a common feature of cancerous states, and an increase in genomic instability is the diagnostic feature of Bloom Syndrome. Bloom Syndrome, a rare disorder characterized by a predisposition to cancer, is caused by mutations of the ..
  7. Machwe A, Lozada E, Xiao L, Orren D. Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins. BMC Mol Biol. 2006;7:1 pubmed
    ..Since this broadens the range of potential physiological substrates for WRN and BLM, our findings have relevance for understanding their functions in vitro and in vivo. ..
  8. Yin J, Sobeck A, Xu C, Meetei A, Hoatlin M, Li L, et al. BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J. 2005;24:1465-76 pubmed
    ..Thus, BLAP75 is an essential component of the BLM-associated cellular machinery that maintains genome integrity. ..
  9. Meetei A, Sechi S, Wallisch M, Yang D, Young M, Joenje H, et al. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol Cell Biol. 2003;23:3417-26 pubmed
    b>Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer...

More Information


  1. Luo G, Santoro I, McDaniel L, Nishijima I, Mills M, Youssoufian H, et al. Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nat Genet. 2000;26:424-9 pubmed
    b>Bloom syndrome is a disorder associated with genomic instability that causes affected people to be prone to cancer. Bloom cell lines show increased sister chromatid exchange, yet are proficient in the repair of various DNA lesions...
  2. Bahr A, De Graeve F, Kedinger C, Chatton B. Point mutations causing Bloom's syndrome abolish ATPase and DNA helicase activities of the BLM protein. Oncogene. 1998;17:2565-71 pubmed
    ..These results provide the first evidence suggesting that the enzymatic activities of the BLM product are implicated in the upholding of genomic integrity. ..
  3. Singh T, Ali A, Busygina V, Raynard S, Fan Q, Du C, et al. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev. 2008;22:2856-68 pubmed publisher
    b>Bloom Syndrome is an autosomal recessive cancer-prone disorder caused by mutations in the BLM gene...
  4. Wang W, Seki M, Narita Y, Sonoda E, Takeda S, Yamada K, et al. Possible association of BLM in decreasing DNA double strand breaks during DNA replication. EMBO J. 2000;19:3428-35 pubmed
    ..The BLM(-/-)/RAD54(-/-) cells showed a slow growth phenotype and an increased incidence of chromosome-type breaks/gaps while each single mutant showed relatively small numbers of chromosome-type breaks/gaps. ..
  5. Hickson I, Davies S, Li J, Levitt N, Mohaghegh P, North P, et al. Role of the Bloom's syndrome helicase in maintenance of genome stability. Biochem Soc Trans. 2001;29:201-4 pubmed
    ..The focus of our work is the Bloom's syndrome gene and its product, BLM. Here, we review the latest information concerning the roles of BLM in the maintenance of genome integrity. ..
  6. Baris H, Kedar I, Halpern G, Shohat T, Magal N, Ludman M, et al. Prevalence of breast and colorectal cancer in Ashkenazi Jewish carriers of Fanconi anemia and Bloom syndrome. Isr Med Assoc J. 2007;9:847-50 pubmed
    Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community...
  7. Kaneko H, Orii K, Matsui E, Shimozawa N, Fukao T, Matsumoto T, et al. BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal. Biochem Biophys Res Commun. 1997;240:348-53 pubmed
    b>Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, sun sensitivity, immunodeficiency and a high predisposition to various types of cancer...
  8. Stavropoulos D, Bradshaw P, Li X, Pasic I, Truong K, Ikura M, et al. The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis. Hum Mol Genet. 2002;11:3135-44 pubmed
    ..Our results identify BLM as the first protein found to affect telomeric DNA synthesis exclusively in human ALT cells and suggest that BLM facilitates recombination-driven amplification of telomeres in ALT cells. ..
  9. Davalos A, Campisi J. Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks. J Cell Biol. 2003;162:1197-209 pubmed
    b>Bloom syndrome (BS) is a hereditary disorder characterized by pre- and postnatal growth retardation, genomic instability, and cancer. BLM, the gene defective in BS, encodes a DNA helicase thought to participate in genomic maintenance...
  10. Ababou M, Dumaire V, Lecluse Y, Amor Gueret M. Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition. Oncogene. 2002;21:2079-88 pubmed
    ..These results are discussed in the light of their potential physiological significance with regard to the role of BLM in the cellular pathways activated by UVC radiation or HU-mediated inhibition of DNA synthesis. ..
  11. Neff N, Ellis N, Ye T, Noonan J, Huang K, Sanz M, et al. The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells. Mol Biol Cell. 1999;10:665-76 pubmed
    b>Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by growth deficiency, immunodeficiency, genomic instability, and the early development of cancers of many types...
  12. Karow J, Constantinou A, Li J, West S, Hickson I. The Bloom's syndrome gene product promotes branch migration of holliday junctions. Proc Natl Acad Sci U S A. 2000;97:6504-8 pubmed
    ..Our results have implications for the role of BLM as an anti-recombinase in the suppression of tumorigenesis. ..
  13. Liu Z, Macias M, Bottomley M, Stier G, Linge J, Nilges M, et al. The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins. Structure. 1999;7:1557-66 pubmed
    ..RNaseD C-terminal) domain is found at the C terminus of many RecQ helicases, including the human Werner and Bloom syndrome proteins. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner...
  14. Mohaghegh P, Hickson I. DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum Mol Genet. 2001;10:741-6 pubmed
    ..Here, we review this network of protein interactions, and the clues that they present regarding the potential roles of RecQ family members in DNA repair, replication and/or recombination pathways. ..
  15. Wang X, Tseng A, Ellis N, Spillare E, Linke S, Robles A, et al. Functional interaction of p53 and BLM DNA helicase in apoptosis. J Biol Chem. 2001;276:32948-55 pubmed
    The Bloom syndrome (BS) protein, BLM, is a member of the RecQ DNA helicase family that also includes the Werner syndrome protein, WRN. Inherited mutations in these proteins are associated with cancer predisposition of these patients...
  16. Du X, Shen J, Kugan N, Furth E, Lombard D, Cheung C, et al. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol. 2004;24:8437-46 pubmed
    ..syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome ..
  17. Furuichi Y. Premature aging and predisposition to cancers caused by mutations in RecQ family helicases. Ann N Y Acad Sci. 2001;928:121-31 pubmed
    ..I also describe a hypothesis of "tissue-specific genomic instability" that accounts for the pathology behind multisymptomatic RecQ helicase syndromes. ..
  18. Dutertre S, Ababou M, Onclercq R, Delic J, Chatton B, Jaulin C, et al. Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase. Oncogene. 2000;19:2731-8 pubmed
    ..Together, these results are consistent with a role of BLM in a replicative (S phase) and/or post-replicative (G2 phase) process. Oncogene (2000). ..
  19. Sengupta S, Linke S, Pedeux R, Yang Q, Farnsworth J, Garfield S, et al. BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination. EMBO J. 2003;22:1210-22 pubmed
    ..Loss of p53 further enhanced the rate of spontaneous sister chromatid exchange (SCE) in Bloom syndrome (BS) cells, but not in their BLM-corrected counterpart, indicating that involvement of p53 in regulating ..
  20. Grabowski M, Svrzikapa N, Tissenbaum H. Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans. Mech Ageing Dev. 2005;126:1314-21 pubmed
    b>Bloom syndrome is caused by mutation of the Bloom helicase (BLM), a member of the RecQ helicase family. Loss of BLM function results in genomic instability that causes a high incidence of cancer...
  21. Koren Michowitz M, Friedman E, Gershoni Baruch R, Brok Simoni F, Patael Y, Rechavi G, et al. Coinheritance of BRCA1 and BRCA2 mutations with Fanconi anemia and Bloom syndrome mutations in Ashkenazi Jewish population: possible role in risk modification for cancer development. Am J Hematol. 2005;78:203-6 pubmed
    Fanconi anemia (FA) and Bloom syndrome (BS) are rare autosomal recessive genetic disorders manifesting in childhood, with a predisposition to cancer development in adolescence and adulthood...
  22. Wu L, Hickson I. The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature. 2003;426:870-4 pubmed
    ..These results have wider implications for our understanding of the process of homologous recombination and the mechanisms that exist to prevent tumorigenesis. ..
  23. Pedrazzi G, Bachrati C, Selak N, Studer I, Petkovic M, Hickson I, et al. The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6. Biol Chem. 2003;384:1155-64 pubmed
  24. Wan L, Han J, Liu T, Dong S, Xie F, Chen H, et al. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proc Natl Acad Sci U S A. 2013;110:10646-51 pubmed publisher
    The Bloom syndrome gene product, BLM, is a member of the highly conserved RecQ family...
  25. Ellis N, Groden J, Ye T, Straughen J, Lennon D, Ciocci S, et al. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell. 1995;83:655-66 pubmed
    ..The presence of chain-terminating mutations in the candidate gene in persons with BS proved that it was BLM. ..
  26. Brosh R, Majumdar A, Desai S, Hickson I, Bohr V, Seidman M. Unwinding of a DNA triple helix by the Werner and Bloom syndrome helicases. J Biol Chem. 2001;276:3024-30 pubmed
    b>Bloom syndrome and Werner syndrome are genome instability disorders, which result from mutations in two different genes encoding helicases...
  27. Myung K, Datta A, Chen C, Kolodner R. SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Nat Genet. 2001;27:113-6 pubmed
    ..This suggests that defects in the suppression of rearrangements involving divergent, repeated sequences may underlie the genome instability seen in BLM and WRN patients and in cancer cases associated with defects in these genes. ..
  28. Mohaghegh P, Karow J, Brosh R, Bohr V, Hickson I. The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res. 2001;29:2843-9 pubmed
    ..We interpret these data in the light of the genomic instability and hyper-recombination characteristics of cells from individuals with Bloom's or Werner's syndrome. ..
  29. Wu L, Chan K, Ralf C, Bernstein D, Garcia P, Bohr V, et al. The HRDC domain of BLM is required for the dissolution of double Holliday junctions. EMBO J. 2005;24:2679-87 pubmed
    ..Furthermore, we show that lysine-1270 of BLM, which resides in the HRDC domain and is predicted to play a role in mediating interactions with DNA, is required for efficient dissolution. ..
  30. German J, Sanz M, Ciocci S, Ye T, Ellis N. Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. Hum Mutat. 2007;28:743-53 pubmed
    b>Bloom syndrome (BS) is caused by homozygous or compound heterozygous mutations in the RecQ DNA helicase gene BLM...
  31. Watt P, Hickson I. Failure to unwind causes cancer. Genome stability. Curr Biol. 1996;6:265-7 pubmed
    ..The recent cloning of the gene defective in individuals with Bloom's syndrome has revealed a link between DNA helicases, genetic instability and a predisposition to cancer. ..
  32. Garkavtsev I, Kley N, Grigorian I, Gudkov A. The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control. Oncogene. 2001;20:8276-80 pubmed
    b>Bloom syndrome is an autosomal recessive disorder associated with mutations in BLM gene encoding protein that belongs to the family of DNA helicases...
  33. Kaneko H, Kondo N. Clinical features of Bloom syndrome and function of the causative gene, BLM helicase. Expert Rev Mol Diagn. 2004;4:393-401 pubmed
    b>Bloom syndrome is a rare autosomal recessive genetic disorder characterized by growth deficiency, unusual facies, sun-sensitive telangiectatic erythema, immunodeficiency and predisposition to cancer...
  34. Hickson I. RecQ helicases: caretakers of the genome. Nat Rev Cancer. 2003;3:169-78 pubmed
    ..So how do RecQ helicases protect against cancer? They seem to maintain genomic stability by functioning at the interface between DNA replication and DNA repair. ..
  35. 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 Res. 2002;62:2766-70 pubmed
    ..This work demonstrates that BS cells, lacking the BLM helicase, process DSBs differently than normal cells and strongly suggests a role for the BLM helicase in aligning microhomology elements during recombinational events in DSB repair. ..
  36. Chabosseau P, Buhagiar Labarch├Ęde G, Onclercq Delic R, Lambert S, Debatisse M, Brison O, et al. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome. Nat Commun. 2011;2:368 pubmed publisher
    Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome. Features of this syndrome include a slowdown in replication speed, defective fork reactivation and high rates of ..
  37. Watt P, Hickson I, Borts R, Louis E. SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics. 1996;144:935-45 pubmed
    ..This contrasts with the telomere maintenance defects of Werner's patients. We conclude that the SGS1 gene product is involved in the maintenance of genome stability in S. cerevisiae. ..
  38. Hanada K, Hickson I. Molecular genetics of RecQ helicase disorders. Cell Mol Life Sci. 2007;64:2306-22 pubmed
    ..Here, we review the current knowledge of the molecular genetics of RecQ helicases, focusing on the human RecQ helicase disorders and mouse models of these conditions. ..
  39. Moens P, Freire R, Tarsounas M, Spyropoulos B, Jackson S. Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom's syndrome, suggest a role in recombination during meiotic prophase. J Cell Sci. 2000;113 ( Pt 4):663-72 pubmed
  40. So S, Adachi N, Koyama H. Absence of p53 enhances growth defects and etoposide sensitivity of human cells lacking the Bloom syndrome helicase BLM. DNA Cell Biol. 2007;26:517-25 pubmed
    The Bloom syndrome helicase BLM and the tumor-suppressor protein p53 play important roles in preserving genome integrity. Here, we knock out the genes for BLM and p53 in a human pre-B-cell line, Nalm-6...
  41. Karow J, Chakraverty R, Hickson I. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J Biol Chem. 1997;272:30611-4 pubmed
  42. Beamish H, Kedar P, Kaneko H, Chen P, Fukao T, Peng C, et al. Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM. J Biol Chem. 2002;277:30515-23 pubmed
    ..These data suggest that ATM and BLM function together in recognizing abnormal DNA structures by direct interaction and that these phosphorylation sites in BLM are important for radiosensitivity status but not for SCE frequency. ..
  43. Yamagata K, Kato J, Shimamoto A, Goto M, Furuichi Y, Ikeda H. Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases. Proc Natl Acad Sci U S A. 1998;95:8733-8 pubmed
    ..We discussed differential roles of BLM and WRN helicases in human cells. BLM- and WRN-bearing yeasts provide new useful models to investigate human BS and WS diseases. ..
  44. Hu P, Beresten S, van Brabant A, Ye T, Pandolfi P, Johnson F, et al. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. Hum Mol Genet. 2001;10:1287-98 pubmed
    ..The data implicate the BLM-Topo IIIalpha complex in the regulation of recombination in somatic cells. ..
  45. Gaymes T, North P, Brady N, Hickson I, Mufti G, Rassool F. Increased error-prone non homologous DNA end-joining--a proposed mechanism of chromosomal instability in Bloom's syndrome. Oncogene. 2002;21:2525-33 pubmed
    ..This aberrant repair is dependent upon the presence of the Ku70/86 heterodimer, a key component in the NHEJ pathway. We propose that aberrant NHEJ is a candidate mechanism for the generation of chromosomal instability in BS. ..
  46. Wu L, Bachrati C, Ou J, Xu C, Yin J, Chang M, et al. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A. 2006;103:4068-73 pubmed
    ..Implications of the conserved ability of type IA topoisomerases to catalyze dissolution and how the evolution of factors such as BLAP75/RMI1 might confer specificity on the execution of this process are discussed. ..
  47. Kusano K, Johnson Schlitz D, Engels W. Sterility of Drosophila with mutations in the Bloom syndrome gene--complementation by Ku70. Science. 2001;291:2600-2 pubmed
    The Drosophila Dmblm locus is a homolog of the human Bloom syndrome gene, which encodes a helicase of the RECQ family. We show that Dmblm is identical to mus309, a locus originally identified in a mutagen-sensitivity screen...
  48. Xu D, Guo R, Sobeck A, Bachrati C, Yang J, Enomoto T, et al. RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev. 2008;22:2843-55 pubmed publisher
    BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3alpha, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for the maintenance of genome stability...
  49. Yankiwski V, Marciniak R, Guarente L, Neff N. Nuclear structure in normal and Bloom syndrome cells. Proc Natl Acad Sci U S A. 2000;97:5214-9 pubmed
    b>Bloom syndrome (BS) is a rare cancer-predisposing disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. BLM, the protein altered in BS, is a RecQ DNA helicase...
  50. Monnat R. Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology. Semin Cancer Biol. 2010;20:329-39 pubmed publisher
    ..Loss of function of three different members has been shown to cause Bloom syndrome (BS), Werner syndrome (WS) and Rothmund-Thomson syndrome (RTS)...
  51. Davies S, North P, Dart A, Lakin N, Hickson I. Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest. Mol Cell Biol. 2004;24:1279-91 pubmed
  52. Killoran M, Keck J. Sit down, relax and unwind: structural insights into RecQ helicase mechanisms. Nucleic Acids Res. 2006;34:4098-105 pubmed
    ..This review summarizes recent studies that relate the structures of RecQ proteins to their biochemical activities. ..
  53. Hoadley K, Xu D, Xue Y, Satyshur K, Wang W, Keck J. Structure and cellular roles of the RMI core complex from the bloom syndrome dissolvasome. Structure. 2010;18:1149-58 pubmed publisher
    BLM, the protein product of the gene mutated in Bloom syndrome, is one of five human RecQ helicases...