Helicases, DNA

Heat of combustion, 113 Heat of hydrogenation, 186 table of, 187 Heat of reaction, 154 Helicase, DNA replication and, 1106 Hell-Volhard-Zelinskii reaction, 849 amino acid synthesis and. 1025 mechanism of, 849 Heme, biosynthesis of, 966 structure of, 946 Hemiacetal, 717 Hemiketal, 717 Hemithioacetal, 1148 Henderson-Hasselbalch equation,... 

Four enzymes are directly involved. They are the UvrABC endonuclease, helicase, DNA polymerase I, and DNA ligase. The first cleaves the DNA strand on both sides of the pyrimidine dimer. The second enzyme removes the single-strand nucleotide segment containing the pyrimidine dimer. DNA polymerase I fills the gap with new DNA, and the nick is sealed by DNA ligase. 

Chromodomain helicase DNA-binding protein 1, interacts with methylated Eys4 on Histone H3... 

Lohman, T. M., Thorn, K., and Vale, R. D., 1998. Staying on track Common features of DNA helicases and microtnbnle motors.. Cell 93 9-12. 

The helicases are enzymes central to life itself. The nature of double-stranded DNA means that before a polymerase can begin to copy the appropriate region of the nucleic acid, the two strands have to be unwound the separation of the two strands is the function of the helicase (Fig. 2). An indication of the significance of this family of enzymes is seen in the so-called Werner syndrome, where the helicase function required in the suppression of inappropriate recombination events is defective and causes genomic instability and cancer (for a review see Cobb and Bjergbaek 2006). 

F%. 2 Herpesvirus DNA-rephcation fork showing the site of action of helicase/primase inhibitors... 

Beard PM, Duffy C, Baines JD (2004) Quantification of the DNA cleavage and packaging proteins UL15 and UL28 in A and B capsids of herpes simplex vims type 1. J Virol 78 1367-1374 Betz UA, Fischer R, Kleymann G, Hendrix M, Rubsamen-Waigmann H (2002) Potent in vivo antiviral activity of the herpes simplex vims primase-helicase inhibitor BAY 57-1293. Antimicrob Agents Chemother 46 1766-1772... 

Townsend L, Devivar R, Turk S, Nassiri M, Drach J (1995) Design, synthesis, and antiviral activity of certain 2,5,6-trihalo-l-(beta-d-ribofuranosyl)benzimidazoles. J Med Chem 38 4098 105 Turlure F, Devroe E, Silver PA, Engelman A (2004) Human cell proteins and human immunodeficiency virus DNA integration. Front Biosd 9 3187-3208 Umehara T, Fukuda K, Nishikawa F, Kohara M, Hasegawa T, NisUkawa S (2005) Rational design of dual-functional aptamers that inhibit the protease and helicase activities of HCV NS3. J Biochem 137 339-347... 

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. 

A replication fotk consists of four components that form in the following sequence (1) the DNA helicase unwinds a short segment of the patental duplex DNA ... 

Two proteins are initially involved in the nonho-mologous rejoining of a ds break. Ku, a heterodimer of 70 kDa and 86 kDa subunits, binds to free DNA ends and has latent ATP-dependent helicase activity. The DNA-bound Ku heterodimer recruits a unique protein kinase, DNA-dependent protein kinase (DNA-PK). DNA-PK has a binding site for DNA free ends and another for dsDNA just inside these ends. It therefore allows for the approximation of the two separated ends. The free end DNA-Ku-DNA-PK complex activates the kinase activity in the latter. DNA-PK reciprocally phos-phorylates Ku and the other DNA-PK molecule, on the opposing strand, in trans. DNA-PK then dissociates from the DNA and Ku, resulting in activation of the Ku helicase. This results in unwinding of the two ends. The unwound, approximated DNA forms base pairs the extra nucleotide tails are removed by an exonucle-... 

Primosome The mobile complex of helicase and primase that is involved in DNA replication. 

An in-depth study of DNA repair systems (Aravind et al., 1999a) has concluded that few, if any, repair proteins occur with identical collinear domain arrangements in all three kingdoms of life. Approximately 10 enzyme families of adenosine triphosphatases (ATPases), photolyases, helicases, and nucleases were identified that are all likely to have been present in the cenancestor. These enzymatic domains are accompanied in DNA repair proteins by numerous regulatory domains. This indicates that the domain architectures of these proteins are labile, with incremental addition and/or subtraction of domains to conserved cores to be a common phenomenon except in the most closely related species. 

Dillingham, M. S., Wigley, D. B., and Webb, M. R. Demonstration of unidirectional single-stranded DNA translocation by PcrA helicase measurement of step size and translocation speed. Biochemistry 2000, 39, 205-12. 

Helicases catalyze the processive separation of duplex DNA into single strands. Despite sharing similarity to helicases, none of the chromatin remodelling factors, with the exception of the INO80 complex, have been shown to catalyze the separation of DNA strands (Shen et al, 2000). Instead, they can translocate on double-stranded (ds) DNA in an ATP-hydrolysis dependent manner and are characterized by their ability to generate superhelical torsional strain in DNA (Havas et al, 2000 Saha et al, 2002 Whitehouse et al, 2003). The crystal structure of Rad54, a member of the SWI/SNF family has been solved for both S. solfataricus and zebrafish which helps to understand the mechanism of the SWI/SNF ATPase domain in remodelling processes (Durr et al, 2005 Thoma et al, 2005). It reveals... 

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