Dna link in medicine

Tyrosyl-DNA phosphodiesterase (TDP) cleaves the phosphodiester bond linking the active site tyrosine residue of topoisomerase I with the 3¢ terminus of DNA in topoisomerase I–DNA complexes which accumulate during treatment of cancer with camptothecin. In yeast, TDP mutation confers a 1000-fold hypersensitivity to camptothecin in the presence of an additional mutation of RAD9 gene [Pouliot, J.J., Yao, K.C., Robertson, C.A. & Nash, H.A. (1999) Science 286, 552–555].

8p research12 01-06-2013 32 2   Download

Formamidopyrimidine-DNA glycosylase (Fpg protein) of Escherichia coliis a DNA repair enzyme that excises oxi-dized purine bases, most notably the mutagenic 7-hydro-8-oxoguanine, from damaged DNA. In order to identify specific contacts between nucleobases of DNA and amino acids from theE. coliFpg protein, photochemical cross-linking was employed using new reactive DNA duplexes containing 5-[4-[3-(trifluoromethyl)-3H-diazirin-3-yl]phe-nyl]-2¢-deoxyuridine dU* residues near the 7-hydro-8-oxoguanosine (oxoG) lesion. ...

5p fptmusic 16-04-2013 31 3   Download

Integrase (IN) is the retroviral enzyme responsible for the integration of the DNA copy of the retroviral genome into the host cellDNA. TheC-terminal domainof INis involved in DNA binding and enzyme multimerization. We previ-ously performed single amino acid substitutions in the C-terminal domain of the avian leukemia and sarcoma vir-uses (ALSV) IN [Moreauet al. (2002). Arch. Virol.147, 1761–1778].

13p fptmusic 12-04-2013 42 4   Download

Base excision repair (BER), a major pathway for the removal of simple lesions in DNA, requires the co-ordinated action of several repair and ancillary proteins, the impairment of which can lead to genetic instability. We here address the role of poly(ADP-ribose) polymerase-1 (PARP-1) in BER. Using anin vitro cross-linking assay, we reveal that PARP-1 is always involved in repair of a uracil-containing oligonucleotide and that it binds to the damaged DNA during the early stages of repair.

0p awards 06-04-2013 43 2   Download

RNA helicase A (RHA), a member of DNA and RNA helicase family containing ATPase activity, is involved in many steps of gene expression such as transcription and mRNA export. RHA has been reported to bind directly to the transcriptional coactivator, CREB-binding protein, and the tumor suppressor protein, BRCA1, and links them to RNAPolymerase II holoenzyme complex. Using yeast two-hybrid screening, we have identified RHA as an interacting molecule of the p65 subunit of nuclear factorjB(NF-jB).

11p awards 05-04-2013 30 4   Download

The chromosomal ends ofLeishmania (Leishmania) ama-zonensis contain conserved 5¢-TTAGGG-3¢ telomeric repeats. Protein complexes that associatein vitro with these DNA sequences,Leishmania amazonensisG-strand telo-meric protein (LaGT1-3), were identified and characterized byelectrophoreticmobilityshift assays andUVcross-linking using protein fractions purified from S100 and nuclear extracts.

14p awards 05-04-2013 37 5   Download

The NMR structure of 2¢,5¢ d(GGGGCCCC) was deter-mined togain insights into the structural differences between 2¢,5¢-and 3¢,5¢-linked DNA duplexes that may be relevant in elucidating nature’s choice of sugar-phosphate links to encode genetic information. The oligomer assumes a duplex with extended nucleotide repeats formed out of mostly N-type sugar puckers. With the exception of the 5¢-terminal guanine that assumes thesyn glycosyl conformation, all other bases prefer theantiglycosyl conformation. Base pairs in the duplex exhibit slide ()1.

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Cellular functions are ultimately linked to metabolic fluxes brought about by thousands of chemical reactions and transport processes. The synthesisof theunderlying enzymes and membrane transporters causes the cell a certain
effort of energyandexternal resources.Considering that those cells should have had a selection advantage during natural evo-lution that enabled them to fulfil vital functions (such as growth, defence against toxic compounds, repair of DNA alterations, etc.)

18p dell39 03-04-2013 34 5   Download

A catalytic turnover of supercoiled DNA (scDNA) transformation medi-ated by topoisomerases leads to changes in the linking number (Lk) of the polymeric substrate by 1 or 2 per cycle. As a substrate of the topoisomeri-zation reaction it is chemically identical to its product; even a single catalytic event results in the quantum leap in the scDNA topology.

8p dell39 27-03-2013 33 4   Download

The contributions of human DNA polymerases (pols)a, dande during S-phase progression were studied in order to elaborate how these enzymes co-ordinate their functions during nuclear DNA replication. Pol d was three to four times more intensely UV cross-linked to nascent DNA in late compared with early S phase, whereas the cross-linking of pols aande remained nearly constant throughout the S phase.

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Replicative helicases are major motor proteins essential for chromosomal DNA replication in prokaryotes. Usually hexameric in solution, their DNA binding property must have different roles at stages ranging from the load-ing onto a branched structure at initiation from the origin to the highly pro-cessive translocation during elongation.

17p cosis54 08-12-2012 38 2   Download

Cisplatin was discovered fortuitously by observing that bacteria present in electrolysis solutions could not divide. Only the cis diamine configuration is active as an antitumor agent. It is hypothesized that in the intracellular environment, a chloride is lost from each position, being replaced by a water molecule. The resulting positively charged species is an efficient bifunctional interactor with DNA, forming Pt-based cross-links.

5p konheokonmummim 03-12-2010 56 3   Download

Nucleotide Repeat Expansion Disorders Several diseases are associated with an increase in the number of nucleotide repeats above a certain threshold (Table 62-6). The repeats are sometimes located within the coding region of the genes, as in Huntington disease or the X-linked form of spinal and bulbar muscular atrophy (SBMA, Kennedy syndrome). In other instances, the repeats probably alter gene regulatory sequences. If an expansion is present, the DNA fragment is unstable and tends to expand further during cell division.

5p konheokonmummim 03-12-2010 63 4   Download