The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J
Marieke LevitusQuinten WaisfiszBarbara C. GodthelpYne de VriesShobbir HussainWouter W. WiegantElhaam Elghalbzouri-MaghraniJûrgen SteltenpoolMartin A. RooimansGerard PalsFré ArwertChristopher G. MathewMałgorzata Z. ZdzienickaKevin HiomJohan P. de WinterHans Joenje
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Bloom syndrome
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Until recently, it had been thought that Fanconi anemia patients were distributed into five complementation groups. However, evidence now points to the existence of three new complementation groups, making the genetic basis of the disease more complicated than anticipated. Also, during the past year, the cloning of a second Fanconi anemia gene by both functional complementation and positional cloning has accelerated research of this disease. Although two genes of the eight characterized complementation groups have now been cloned, the function of their gene products still needs to be identified.
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Bloom (BLM) helicase is an important member of the RecQ family of DNA helicases that plays a vital role in the maintenance of genomic stability. The defect of BLM helicase leads to a human genetic disorder called Bloom syndrome, characterized by genomic instability, specific phenotypic features, and a predisposition to many types of cancer. The predisposition to cancer caused by BLM helicase is due to defects in important DNA metabolic pathways such as replication, recombination, and repair. Therefore, the aim of this work was to investigate the effects of two prenylated chalcones, WZH-10 and WZH-43, on the expression of BLM helicase in prostate cancer cells, as well as the biological activity of the purified BLM helicase from cancer cells. This might lead to a better understanding of the role of BLM helicase in the aforementioned DNA metabolic pathways that directly influence chromosomal integrity leading to cancer. The results indicated that the two prenylated chalcones inhibited the growth of prostate cancer cells PC3 by inducing apoptosis and arresting the cell cycle. However, they only inhibited the protein expression of BLM helicase without regulating its transcriptional expression. In addition, they did not significantly regulate the expression of the homologous family members WRN and RECQL1, although the DNA unwinding and ATPase activity of BLM helicase were inhibited by the two prenylated chalcones. Finally, a negligible effect was found on the DNA-binding activity of this enzyme. These results demonstrated that prenylated chalcones can be an effective intervention on the expression and function of the BLM helicase protein in cancer cells to inhibit their growth. Therefore, they might provide a novel strategy for developing new anti-cancer drugs targeting the genomic stability and DNA helicase.
Bloom syndrome
RNA Helicase A
RecQ helicase
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Lymphoblast
Chromosome instability
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RecQ helicase
Bloom syndrome
Werner syndrome
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BLM helicase is an important member of the RecQ family DNA helicase and plays an important role in the maintenance of genetic stability,and its mutation could lead to the Bloom’s syndrome.Bloom’s syndrome(BS) is a rare,autosomal recessive genetic disorder,and patients is easy to sick the most types of cancers.The effects of pH,reaction time,and concentrations of NaCl on the stability and ATP activity of BLM helicase were investigated by ultraviolet absorption spectroscopy.The results indicated that the conformation and ATP activity of BLM helicase were affected by the pH,the effects of alkaline environment on which were greater impact than acid environment.The conformation and ATP activity of BLM helicase had a few of effects in dilution process.The NaCl solution had few effects on the conformation and ATP activity of BLM helicase when the concentrations were less than 500mmol/L,but the conformation and ATP activity were affected when the concentrations were more than 500mmol/L.These results may provide the associated materials to study the interaction of small-molecule drugs and BLM helicase.
Bloom syndrome
RNA Helicase A
RecQ helicase
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Bone marrow failure
FANCA
Lymphoblast
Cell fusion
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Bloom syndrome
RecQ helicase
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RecQ5 is one of five RecQ helicase homologs identified in humans. Three of the human RecQ homologs (BLM, WRN and RTS) have been linked to autosomal recessive human genetic disorders (Bloom syndrome, Werner syndrome and Rothmund-Thomson syndrome, respectively) that display increased genomic instability and cause elevated levels of cancers in addition to other symptoms. To understand the role of RecQ helicases in maintaining genomic stability, the WRN, BLM and Escherichia coli RecQ helicases have been characterized in terms of their DNA substrate specificity. However, little is known about other members of the RecQ family. Here we show that Drosophila RECQ5 helicase is a structure-specific DNA helicase like the other RecQ helicases biochemically characterized so far, although the substrate specificity is not identical to that of WRN and BLM helicases. Drosophila RECQ5 helicase is capable of unwinding 3' Flap, three-way junction, fork and three-strand junction substrates at lower protein concentrations compared to 5' Flap, 12 nt bubble and synthetic Holliday junction structures, which can be unwound efficiently by WRN and BLM.
RecQ helicase
Bloom syndrome
Werner syndrome
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