• ATPase that is strongly stimulated by either single- or double-stranded DNA
• BLM exhibits ATP- and Mg2+-dependent DNA helicase activity that displays 3'-5' polarity
• can unwind G4 DNA (BLM G4 DNA unwinding activity is ATP-dependent and requires a short 3' region of single-stranded DNA)
• G4 DNA is a preferred substrate of the BLM helicase, as measured both by efficiency of unwinding and by competition. 
  
• Single amino acid substitutions found in Bloom's Syndrome (BS) cells, abolish both ATPase and helicase activities of this protein, indicating that defects in these BLM functions may be primarily responsible for BS establishment.
  
• The first 431 amino acids of the N terminal domain as a fusion to a hexahistidine tag appear to form hexamers and dodecamers. Treatment with EDTA and DTT prevents and disrupt this aggregation.
• BLM forms hexameric ring structures with an overall diameter of approximately 13 nm surrounding a central hole of approximately 3.5 nm diameter as visualized by electron microscopy. Chromatography studies indicate that the majority of enzymatically active BLM has an apparent molecular mass of > 700 kDa

• Mutations in the blm gene results in genomic instability that causes Bloom's Syndrome (BS), a rare autosomal recessive genetic disorder characterized by lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted growth infertility and immunodeficiency. Bloom's Syndrome patients are highly predisposed to cancers.
  
• Introduction of the previously cloned BLM gene into BLM cells yields correction of the chromosome instability and slow growth phenotypes.
• BS cells are characterized by an increased rate of sister chromatid exchange (SCE)
• blm gene has been mapped to human chromosome 15 band q26.1
• translocates into the nucleus (the distal arm of the bipartite basic residues in the C-terminus of the BLM protein is essential for targeting the nucleus)
• BLM is localized to punctate nuclear structures (central helicase domain is necessary for producing the punctate pattern)
• BLM is targeted to specific nuclear structures and its expression is enhanced during cell growth
• BLM colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes
• proteins from three missense alleles lack DNA helicase activity
• BLM complements a phenotype of a Saccharomyces cerevisiae sgs1 top3 strain, but the missense alleles do not
• Blm could also be involved in transcription regulation.
• is apparently involved in the maintenance of the stability of DNA.
• BLM protein may also play a role in the detection of certain types of DNA damage and in the cellular response to that damage.
• Enzymatic activities of the BLM product (Helicase and ATPase) are implicated in the upholding of genomic integrity.
  
• BLM and WRN appear to play distinct in processes such as DNA repair and recombination as suggested by the nucleolar localization of WRN, its invariant expression during the cell cycle, and the lack of interaction between BLM and WRN

• RecQ (E.coli)
• SGS1 (S. cerevisiae)
• DMBLM (D. melanogaster)
• RAD12+ (S. pombe)

Straughen J, Ciocci S, Ye TZ, Lennon DN, Proytcheva M, Alhadeff B, Goodfellow P, German J, Ellis NA, and Groden J. Physical mapping of the bloom syndrome region by the identification of YAC and P1 clones from human chromosome 15 band q26.1. Genomics 35, 118-128 (1996).

Ellis NA and German J. Molecular genetics of Bloom's syndrome. Hum. Mol. Genet. 5 Spec No:1457-1463 (1996).

Kaneko H, Inoue R, Yamada Y, Sukegawa K, Fukao T, Tashita H, Teramoto T, Kasahara K, Takami T, and Kondo N. Microsatellite instability in B-cell lymphoma originating from Bloom syndrome. Int. J. Cancer 69, 480-483 (1996).

Kaneko H, Orii KO, Matsui E, Shimozawa N, Fukao T, Matsumoto T, Shimamoto A, Furuichi Y, Hayakawa S, Kasahara K, and Kondo N. BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal. Biochem. Biophys. Res. Commun. 240, 348-353 (1997).

Giesler T, Baker K, Zhang B, McDaniel LD, and Schultz RA. Correction of the Bloom syndrome cellular phenotypes. Somat. Cell Mol. Genet. 23, 303-312 (1997).

Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, and 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. Genet. 6, 1427-1434 (1997).

Karow JK, Chakraverty RK, and Hickson ID. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J. Biol. Chem. 272, 30611-30614 (1997).

Straughen JE, Johnson J, McLaren D, Proytcheva M, Ellis N, German J, and Groden J. A rapid method for detecting the predominant Ashkenazi Jewish mutation in the Bloom's syndrome gene. Hum. Mutat. 11, 175-178 (1998).

Sack SZ, Liu Y, German J, and Green NS. Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase. Clin. Exp. Immunol. 112, 248-254 (1998).

Calin G, Herlea V, Barbanti-Brodano G, and Negrini M. The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors. Cancer Res. 58, 3777-3781 (1998).

Sun H, Karow JK, Hickson ID, and Maizels N. The Bloom's syndrome helicase unwinds G4 DNA. J. Biol. Chem. 273, 27587-27592 (1998).

Ellis NA, Ciocci S, Proytcheva M, Lennon D, Groden J, and German J. The Ashkenazic Jewish Bloom syndrome mutation blmAsh is present in non-Jewish Americans of Spanish ancestry. Am. J. Hum. Genet. 63, 1685-1693 (1998).

Collister M, Lane DP, and Kuehl BL. Differential expression of p53, p21waf1/cip1 and hdm2 dependent on DNA damage in Bloom's syndrome fibroblasts.Carcinogenesis 19, 2115-2120 (1998).

Shahrabani-Gargir L, Shomrat R, Yaron Y, Orr-Urtreger A, Groden J, and Legum C. High frequency of a common Bloom syndrome Ashkenazi mutation among Jews of Polish origin. Genet. Test. 2, 293-296 (1998).

Neff NF, Ellis NA, Ye TZ, Noonan J, Huang K, Sanz M, and Proytcheva M. 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).

Ellis NA, Proytcheva M, Sanz MM, Ye TZ, and 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).

Walpita D, Plug AW, Neff NF, German J, and Ashley T. Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes. Proc. Natl. Acad. Sci. USA 96, 5622-5627 (1999)

Gharibyan V and Youssoufian H. Localization of the bloom syndrome helicase to punctate nuclear structures and the nuclear matrix and regulation during the cell cycle: Comparison with the werner's syndrome helicase. Mol. Carcinog. 26, 261-273 (1999).

Karow JK, Newman RH, Freemont PS, and Hickson ID. Oligomeric ring structure of the Bloom's syndrome helicase. Curr. Biol. 9, 597-600 (1999).

Roa BB, Savino CV, and Richards CS. Ashkenazi Jewish population frequency of the Bloom syndrome gene 2281 delta 6ins7 mutation. Genet. Test. 3, 219-221 (1999)

Beresten SF, Stan R, van Brabant AJ, Ye T, Naureckiene S, and Ellis NA. Purification of overexpressed hexahistidine-tagged BLM N431 as oligomeric complexes. Protein Expr. Purif. 17, 239-248 (1999)

Kaneko H, Matsui E, Fukao T, Kasahara K, Morimoto W, and Kondo N. Expression of the BLM gene in human haematopoietic cells. Clin. Exp. Immunol. 118, 285-289 (1999)

Mouse BLM:

Seki T, Wang WS, Okumura N, Seki M, Katada T, and Enomoto T. cDNA cloning of mouse BLM gene, the homologue to human Bloom's syndrome gene, which is highly expressed in the testis at the mRNA level. Biochim. Biophys. Acta 1398, 377-381 (1998).

Chester N, Kuo F, Kozak C, O'Hara CD, and 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).

Bahr A, De Graeve F, Kedinger C, and Chatton B.Point mutations causing Bloom's syndrome abolish ATPase and DNA helicase activities of the BLM protein. Oncogene 17, 2565-2571 (1998).

BLM / Bloom syndrome reviews:

Bamezai, R. Bloom syndrome: is the gene mapped to the point? Indian J. Exp. Biol. 34, 298-301 (1996).

Watt PM and Hickson ID. Failure to unwind causes cancer. Genome stability. Curr. Biol. 6, 265-267 (1996).