CFS-1686 (chemical name (E)-N-(2-(diethylamino)ethyl)-4-(2-(2-(5-nitrofuran-2-yl)vinyl)quinolin-4-ylamino)benzamide) inhibits cell proliferation and triggers late apoptosis in prostate cancer cell lines. Comparing the effect of CFS-1686 on cell cycle progression with the topoisomerase 1 inhibitor camptothecin revealed that CFS-1686 and camptothecin reduced DNA synthesis in S-phase, resulting in...

Dna2 is a nuclease/helicase with proposed roles in DNA replication, double-strand break repair and telomere maintenance. For each role Dna2 is proposed to process DNA substrates with a 5'-flap. To date, however, Dna2 has not revealed a preference for binding or cleavage of flaps over single-stranded DNA. Using DNA binding competition assays we found that Dna2 has substrate structure specificity...

The RAG (recombination-activating gene) complex is responsible for the generation of antigen receptor diversity by acting as a sequence-specific nuclease. Recent studies have shown that it also acts as a structure-specific nuclease. However, little is known about the factors regulating this activity at the genomic level. We show in the present study that the proximity of a V(D)J nonamer to hete...

Cleavage of linear duplex DNA by purified vaccinia virus DNA topoisomerase I occurs at a conserved sequence element (5'-C/T)CCTT decreases) in the incised DNA strand. Oligonucleotides spanning the high affinity cleavage site CCCTT at nucleotide 2457 in pUC19 DNA are cleaved efficiently in vitro, but only when hybridized to a complementary DNA molecule. As few as 6 nucleotides proximal to the cl...

Novel copper(ii) complexes bearing 2,2'-bipyridine (bpy) derivatives with adenine, thymine and uracil nucleobases [Cu(L(1))Cl(2)].2H(2)O (1), [Cu(L(2))Cl(2)] (2) and [Cu(L(3))Cl(2)].H(2)O (3) (L(1) = 5,5'-Di[N9-adenylmethyl]-2,2'-bipyridine, L(2) = 5,5'-Di[N1-thyminylmethyl]-2,2'-bipyridine and L(3) = 5,5'-Di[N1-uracilmethyl]-2,2'-bipyridine) were synthesized and characterized. Structure simula...

A pair of single-molecule photo-responsive DNA nanoscissors for DNA cleavage based on the regulation of substrate binding affinity was designed and fabricated. Compared with other DNA nanomachines, our DNA nanoscissors have the advantages of a clean switching mechanism, as well as robust and highly reversible operation.

The Pax3 protein has two DNA binding domains, a Paired domain (PD) and a paired-type Homeo domain (HD). Although the PD and HD can bind to cognate DNA sequences when expressed individually, genetic and biochemical data indicate that the two domains are functionally interdependent in intact Pax3. The mechanistic basis of this functional interdependence is unknown and was studied by protease sens...

Type IB topoisomerases unwind positive and negative DNA supercoils and play a key role in removing supercoils that would otherwise accumulate at replication and transcription forks. An interesting question is whether topoisomerase activity is regulated by the topological state of the DNA, thereby providing a mechanism for targeting the enzyme to highly supercoiled DNA domains in genomes. The ty...

A key step in the DNA transport by type II DNA topoisomerase is the formation of a double-strand break with the enzyme being covalently linked to the broken DNA ends (referred to as the cleavage complex). In the present study, we have analyzed the formation and structure of the cleavage complex catalyzed by Sufolobus shibatae DNA topoisomerase VI (topoVI), a member of the recently described typ...

Ternary iron(II) complexes [Fe(L)B](PF6)2 (1-3), where L is formed from FeCl3 mediated cyclization of N,N'-(2hydroxypropane-1,3-diyl)bis(pyridine-2-aldimine) (L) and B is a phenanthroline base, viz. 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 3), are synthesized and complex 1 is structurally characterized by X-ray crysta...