Contact sites of AraC protein to the regulatory site araI of the Escherichia coli araBAD operon have been determined by the chemical-interference technique. DNA fragments were chemically modified an average of once per molecule, and fragments that no longer bound AraC were separated by gel electrophoresis from the DNA fragments still able to bind the protein. The contact sites were then determi...

Depurination/depyrimidation binding-interference experiments (missing contact probing) identified specific candidate residue-base interactions lost by mutants of Escherichia coli L-arabinose operon regulatory protein, AraC, to one of its binding sites, araI. These candidates were then checked more rigorously by comparing the affinities of wild-type and alanine-substituted AraC protein to varian...

BACKGROUND Circulating nucleosomes are elevated in the blood of patients with malignant and non-malignant diseases. Here, we investigated the nature and the dynamics of their release in functional cell studies. MATERIALS AND METHODS Leukemia blasts were exposed to the intrinsic inducers of apoptotic cell death, cytosine arabinoside (AraC; 10 μg/ml) and etoposide (50 μg/ml), and cell death mar...

Chemoresistance to anticancer drugs is a major issue in the successful treatment of acute myeloid leukemia (AML). In this study, we developed an AML cell line (AML-2/IDAC) that is resistant to treatment with a combination of idarubicin and cytosine arabinoside (Id/AraC) by chronic exposure for more than 3 months. We then investigated the ability of indomethacin to alleviate the chemoresistance ...

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal disorders characterized by quantitative and qualitative abnormalities of hematopoiesis [1, 2]. Up to 30% of cases eventually develop into acute nonlymphocytic leukemia (ANLL). Previous observations by us and others have demonstrated a frequent (30%) activation of the N-ras oncogene in ANLL [3-6]. The involvement of the dif...

PURPOSE Successful treatment of acute myeloid leukemia (AML) remains a therapeutic challenge, with a high percentage of patients suffering from persistent or relapsed disease. Resistance to drug therapy can develop from increased drug export and/or altered intracellular signaling. Both mechanisms are mediated by the efflux transporters ABCC4 (MRP4), ABCC5 (MRP5), and ABCC11 (MRP8), which are in...

A DNA-directed cell-free system to study the L-arabinose BAD operon has been further developed so that the rate of synthesis of enzymes coded for by the structural genes in the operon in vifro is about 5 % the in vivo rate. L-Arabinose isomerase and L-ribulokinase, the products of the araA and araB genes, are synthesized at the same rate, demonstrating that the operon is coordinately expressed ...

Cytosine arabinoside (araC) has proven efficacy in acute myeloid leukemia (AML), but its place in the treatment of acute lymphoblastic leukemia (ALL) and T lymphoblastic lymphoma is uncertain. The therapeutic potential of araC has been assessed in patients with AML, ALL, and T lymphoblastic lymphoma by measuring the conversion of araC to its active metabolite, the 5'-triphosphate of araC (araCT...

The AraC/XylS family of transcription activator proteins is defined by a 100-amino-acid region of sequence similarity (15) that forms an independently folding domain containing two helix-turn-helix (HTH) DNA binding motifs. A recent database search (http://hits.isb-sib.ch) (35) by the author using the AraC/XylS family profile (PS01124) (15) identified 830 family members! A number of AraC/XylS f...

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of...