DNA ases

It should be pointed out that when using ethidium bromide the sensitivity of the assays varies depending on the physical state of the nucleic acids (see Table I). Ethidium does not discriminate between RNA and DNA, although dyes are available which bind DNA exclusively, so the relative amounts of each may be determined by taking two sets of measurements. Alternatively, nucleases (DNA-ase or RNA-ase) can be used to exclusively remove one or the other in a mixture. Nucleic acids from different sources (see Table II) also show a variation in sensitivity, and the fluorescence assay lacks the selectivity of the hybridization technique. Nevertheless, for rapid screening or quality-control applications the fluorescence assay is still the method of choice. 

TS. Tabaehnik, J., Perlish, J. S., Freed, R. M., and Chang, L. F., Increased epidermal DNA-ase I activity after clipping or plucking of hair during wound healing. J. Invest. Dermatol. 46, 555-560 (1966). 

T6. Tabaehnik, J., and Labadie, J. H., Increased activity of skin surface DNA-ase I after beta-irradiation injury or clipping of guinea pig hair. J. Invest. Dermatol. 65, 89-93 (1970). 

Ribonucleases, DNA-ase, 5 nucleotidase Act against nucleic acids and phosphate monoesters... 

DNA %ase The enzyme which catalyzes joining of the 5 and y termini of two single-stranded DNA fragments in a double-stranded DNA by forming a phosphodiester bond. 

Examples (a) nucleosome K Huger, AW Mader, RK Richmond, DF Sargent, TJ Richmond. Nature 389 251-260, 1997 (b) DNA polymerases CA Brautigam, TA Steitz. Curr. Opin. Struct. Biol. 8 54-63, 1998 (c) single-stranded binding protein Y Shamoo, AM Friedman, MR Parsons, WH Konigsberg, TA Steitz. Nature 376 362-366, 1995 (d) restriction endonucleases RA Kovall, BW Matthews. Curr. Opin. Chem. Biol. 3 578-583, 1999 (e) DNA lig-ase S Shuman. Structure 4 653-656, 1996 (f) DNA helicases MC Hall, SW Matson. Mol. Microbiol. 34 867-877, 1999 (g) zinc-finger proteins Y Choo, JW Schwabe. Nat. Struct. Biol. 5 253-255, 1998. 

Figure 36-24. Nucleotide excision-repair. This mechanism is employed to correct larger defects in DNA and generally involves more proteins than either mismatch or base excision-repair. After defect recognition (indicated by XXXX) and unwinding of the DNA encompassing the defect, an excision nuclease (exinucle-ase) cuts the DNA upstream and downstream of the defective region. This gap is then filled in by a polymerase (5/e in humans) and religated.

DNA in each chromosome is exactly replicated according to the mles of base pairing during the S ph ase of the cell cycle. 

Aeromonas, DNA-based biosensor, 3 807 AeroSizer, 78 150—151 Aerosol containers, 7 781-782 Aerosol dispersions, 7 774-775 Aerosol drug dosage forms, 78 717 Aerosol emulsions, 7 773, 774 Aerosol flow reactors, 77 211-212 Aerosol foams, 7 773, 774 Aerosol packaging, 7 771 Aerosol pastes, 7 775 Aerosols, 7 769-787 8 697 economic aspects, 7 786 filling, 7 785-786 formulation, 7 771-780 product concentrate, 7 772-775 propellants, 7 775-781 U.S. production, 1985-2000, 7 770t Aerosol solutions, 7 772-773 Aerosol solvent extraction system (ASES), 24 17, 18... 

DNA ligase (NAD+) [EC 6.5.1.2] (also referred to as polydeoxyribonucleotide synthase (NAD+), polynucleotide ligase (NAD+), DNA repair enzyme, and DNA join-ase) catalyzes the reaction of NAD+ with (deoxyribo-nucleotide) and (deoxyribonucleotide) to produce AMP, nicotinamide nucleotide, and (deoxyribonucleo-tide)( +m). This forms a phosphodiester at the site of a single-strand break in duplex DNA. RNA can also act as substrate to some extent. 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

WARNING Administer only under sup vision of a healthcare provider experienced in leukemia and in an institution w/ resources to maintain a pt compromised by drug tox Uses Acute leukemias CML in blast crisis, breast CA Action DNA intercalating agent i DNA topoisom ases I II Dose (Per protocol) 10-12 mg/mVd for 3-4 d 4- in renal/hepatic impairment Caution [D, -] Contra Bilirubin >5 mg/dL, PRO Disp Inj 1 mg/mL (5, 10, 20 mg vials) SE X BM, cardiotox, N/V, mucositis, alopecia, IV site Rxns, rarely -1- renal/hepatic Fxn Interactions Myelo-suppression W/ antineoplastic drugs and radiation therapy -1- effects OF live virus vaccines EMS Monitor for S/Sxs of Infxn OD May cause N/V, t Infxn risk and cardio/GI tox symptomatic and supportive... 

B viral polym ase, causes viral DNA chain tOTnination Dose HIV Adults Peds >16y. 150 mg PObidor 300mgPO daily <16y. 4mg/kg POhiAHBV Adults. 

Penciclovir (Denavir) [Antiviral] U e Herpes simplex (herpes labialis/ cold sores) Action Competitive inhibitor of DNA polym ase Dose Apply at 1st sign of lesions, then q2h while awake x 4 d Caution [B, /-] Contra Allergy, previous Rxn to famciclovir Disp Cream SE Erythema, HA EMS None OD Unlikely to cause life-threatening Sxs... 

Topotecan (Hycamtin) [Antineoplastic] WARNING Chemo precautions, for use by healthcare provides familiar w/ chemo agents, BM suppression possible Uses Ovarian CA (cisplatin-refractory), CCTvical Ca, NSCLC, sarcoma, ped NSCLC Action Topoisom ase I inhibitor -1- DNA S5mth Dose 1.5 mg/mVd as a 1-h IV inf X 5 d, r eat q3wk -1- w/ renal impair Caution [D, —]... 

Many enzymes have been named by adding the suffix -ase to the name of their substrate or to a word or phrase describing their activity. Thus urease catalyzes hydrolysis of urea, and DNA polymerase catalyzes the polymerization of nucleotides to form DNA. Other enzymes were named by their discovers for a broad func-... 

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