Replication complexes

RNA decoys from HCV stem-loop structures in NS5B coding region sequester replication complexes HCV (Zhang et al. 2005)... 

Nasmyth If you reactivated the kinase, given that the kinase inhibits prereplication complex formation, this would do the job. There are two ways of preventing replication one is not to make the components of the pre-replication complex, the other is to keep the kinase high, which inhibits that formation. This could be an explanation of the Nenopus work. 

Nasmyth We know that in G2, where HI kinase is not high, we know that there is sufficient cdk activity to inhibit pre-replication complex formation. If it has gone down at interphase, there still could be a lot of cdk present. 

Gautier As far as the pre-replication complex is concerned, just looking at the level of Cdc6/Cdcl 8 is not going to tell us anything, because in Nenopus eggs all the maternal protein is already made for 10 divisions. 

DNA replication proceeds in both directions from the replication origin (bidirectional), which means you need to form two sets of replication complexes. Each replication complex moves away from the origin (in opposite directions), unwinding and replicating both strands at each replication fork. 

Applegren N, Hickey RJ, Kleinschmidt AM, Zhou Q, Coll J, Wills P, Swaby R, Wei Y, Quan JY, Lee MY et al. (1995) Further characterization of the human cell multiprotein DNA replication complex. J Cell Biochem 59 91-107... 

Once the replication fork is established, other proteins begin assembling the functional DNA replication complex. 

Control of origin activity occiu s via specific protein complexes that are boimd at certain times of the cell cycle to a replication origin. For replication initiation, two states of this protein complex are important, known as the pre-rephcation complex and the post-replication complex. 

The pre-replication complex (pre-RC) is formed diming anaphase and is inherited by the sister chromatids. Upon entry into S phase, the pre-RC must be disrupted for initiation to occur. If initiation begins, the pre-RC changes to the post-rephcation complex state, which does not permit further initiation. 

Marked variations in IFT aging behavior of replicate complex coacervate phase/citrus oil interfaces were observed occasionally. Figure 13 illustrates an example of this. Two IFT aging curves for the G/A complex coacervate phase/lemon oil 2 interface differ by 0.3 to 1.3 mJ/m2 throughout the 1.3-1.5 hour of aging needed for the IFT to reach a value too low to measure. A third run gave a value too low to measure immediately after the interface was formed. This type of behavior was encountered periodically, especially with complex coacervate phase/citrus oil interfaces at 40-45 C. Experimental technique probably caused most of these observations since it is difficult to place the Wilhelmy plate at complex coacervate phase/ citrus oil interfaces. However, the possibility that an IFT too low to measure immediately after formation of an interface is a characteristic feature of some complex coacervate phase/citrus oil interfaces at 40° and 34°C cannot be completely ruled out. 

Two other protein complexes also function in eukaryotic DNA replication. RPA (replication protein A) is a eukaryotic single-stranded DNA-binding protein, equivalent in function to the E. coli SSB protein. RFC (replication/actor (J) is a clamp loader for PCNA and facilitates the assembly of active replication complexes. The subunits of the RFC complex have significant sequence similarity to the subunits of the bacterial clamploading (y) complex. 

Polynucleotide polymerases, or nucleotidyl transferases, are enzymes that catalyze the template-instructed polymerization of deoxyribo- or ribonu-cleoside triphosphates into polymeric nucleic acid - DNA or RNA. Depending on their substrate specificity, polymerases are classed as RNA- or DNA-dependent polymerases which copy their templates into RNA or DNA (all combinations of substrates are possible). Polymerization, or nucleotidyl transfer, involves formation of a phosphodiester bond that results from nucleophilic attack of the 3 -OH of primer-template on the a-phosphate group of the incoming nucleoside triphosphate. Although substantial diversity of sequence and function is observed for natural polymerases, there is evidence that many employ the same mechanism for DNA or RNA synthesis. On the basis of the crystal structures of polymerase replication complexes, a two-metal-ion mechanism of nucleotide addition was proposed [1] during this two divalent metal ions stabilize the structure and charge of the expected pentacovalent transition state (Figure B.16.1). 

DNA replication at the site opposite to the adduct. In addition, DNA polymerase P was able to elongate the arrested replication products of the other three DNA polymerases in their presence, thus showing its capacity to successfully compete with them at a stalled replication complex. These results suggest that only DNA polymerase P, possibly because of its distributive mode of action and simple subunit composition, can productively associate with the primer/template junction formed at the base preceding the d(GpG) adduct and continue DNA elongation in a reaction which includes the replicative DNA polymerases. 

Simbulan-Rosenthal CM, Rosenthal DS, Hilz H, Hickey R, Malkas L, Applegren N, Wu Y, Bers G, and Smulson ME (1996) The expression of poly(ADP-ribose) polymerase during differentiation-linked DNA replication reveals that it is a component of the multiprotein DNA replication complex. Biochemistry 35,11622-33. 

Enhanced tolerance to DNA adducts has been fonnd in some cisplatin-resistant ceUs. Mechanisms that are involved are enhanced postreplicative bypass the ability of the replication complex to synthesize DNA downstream a cisplatin-indnced lesion and defects in the repair process named mismatch repair (MMR). 

In addition, three enzymes involved in DNA replication, including DNA primases, prokaryotic DNA topoisomerase I and some hexameric DNA helicases, are also classic zinc-ribbon proteins. In bacteriophage DNA primases, mutations of the zinc-binding residues abrogate the synthesis of RNA primers for lagging strand DNA synthesis. Strikingly, each subunit of the mini-chromosomal maintenance (MCM) protein, a heterohexameric helicase that initiates DNA replication in S. cerevisiae, contains an independently folded zinc-ribbon domain that appears to stabilize the dodecameric structure (a dimer of hexamers) of this replication complex. ... 

Doublie S, Tabor S, Long AM, Richardson CC, Ellenberger T. Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 A resolution. Nature 1998 391 251-258. 

McHenry CS. DNA polymerase III holoenzyme. Components, structure, and mechanism of a true replicative complex. J. Biol. Chem. 1991 266 19127-19130. 

McHenry CS, Johanson KO. DNA polymerase m holoenzyme of Escherichia coli an asymmetric dimeric replicative complex containing distinguishable leading and lagging strand polymerases. Adv. Exp. Med. Biol. 1984 179 315-319. 

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