84-1090-91　Bloom Syndrome (BLM, BS, RECQ2, RECQL2) 100ul　B2163-08

特徴

• BLM, a member of the RecQ family of DNA helicases, is part of the BRCA1-associated genome surveillance complex (BASC) that responds to DNA damage, stalled replication forks and S phase arrest (1-4).
• Phosphorylation of BLM helicase at Thr99 and Thr122 occurs in response to genotoxic stress (4), and phosphorylation of Ser144 appears to be important in regulating chromosome stability during mitosis (5).
• Typical BLM protein resides in the nucleus and forms part of a dynamic protein complex that acts in response to DNA damage during specific periods of the cell cycle (6).
• Although RecQ helicases are rarely considered as essential enzymes, they function at the interface between DNA recombination and repair and are required for global genome stability maintenance.
• Mutations in BLM helicase are responsible for development of Bloom Syndrome, a recessive genetic disorder clinically characterized by short stature, immunodeficiency and elevated risk of malignancy (7).
• Similar alterations to genes encoding the related RecQ helicases RecQ4 and WRN also result in recessive genetic disorders associated with genomic instability (8,9).
• Cells from Bloom Syndrome patients exhibit genomic instability and increased frequency of sister chromatid exchange (10).
• Mutations of the gene for BLM have previously been associated with Bloom's syndrome, a disorder characterized by growth deficiency, chromosomal instability, and a predisposition to various cancers.
• Studies have implicated the BLM protein, an enzyme with potential roles in DNA replication, recombination, and chromosome segregation.
• Bloom syndrome is a rare autosomal recessive disorder characterized by telangiectases and photosensitivity, growth deficiency of prenatal onset, variable degrees of immunodeficiency, and increased susceptibility to neoplasms of many sites and types.
• The New York dermatologist David Bloom first described the syndrome in 1954.
• The syndrome is caused by a mutation in the gene designated BLM, traced to band 15q26.1.
• The protein encoded by the normal gene has DNA helicase activity and functions in the maintenance of genomic stability.
• Increased sister chromatid exchanges and chromosomal instability also occur, which is assumed to be responsible for the phenotype and the cancer predisposition.
• In 1989, Nicotera et al suggested that the major biochemical defect in persons with Bloom syndrome is chronic overproduction of the superoxide radical anion.
• They thought that inefficient removal of peroxide might be responsible for the high rates of sister chromatid exchange and chromosomal damage in Bloom syndrome cells.
• More than 170 case reports have been made.
• The frequency of parental consanguinity is much greater than in the general population.
• Bloom syndrome is more common in Ashkenazi Jews but has been reported in Japan and other countries.
• Early diagnosis of leukemia is, at present, not known to improve the chances of curative therapy.
• Frequent hematologic examinations in children is not advised for fear of untoward psychologic effects.
• Allogeneic marrow grafting has not been performed in Bloom syndrome patients.
• Men with Bloom syndrome are sterile; women have reduced fertility and a shortened reproductive span.
• Bloom syndrome patients who become pregnant are at high risk for premature delivery.
• Intelligence is usually normal, although mild deficiency has occurred in a few affected persons.
• Diabetes occurs in approximately 10% of individuals with Bloom syndrome.
• Bloom syndrome is more common in eastern European Ashkenazi Jews.
• The male-to-female ratio is 1.3:1.
• This condition occurs in the first few months of life.
• Applications:Suitable for use in Western Blot.
• Other applications not tested.
• Recommended Dilution:Western Blot: 1:1000, incubate membrane with diluted antibody in 5% w/v BSA, 1X TBS, 0.1% Tween-20 at 4°C with gentle shaking, overnight
• Optimal dilutions to be determined by the researcher.
• Storage and Stability:For long-term storage, aliquot and store at -20°C.
• Aliquots are stable for at least 12 months at -20°C.
• For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
• Further dilutions can be made in assay buffer.