Replicating sequences

ARS Autonomously replicating sequence the origin of replication in yeast. 

One limit to this beautiful chemistry hes in the requirement of selfcomplementarity of the self-replicating sequences. The more general case of a template working by complementarity was also investigated by von Kiedrowski s group (Sievers et al, 1994). As noted by Burmeister (1998), the underlying principle in this case is a cross-catalytic reaction in which one strand acts as a catalyst for the formation of the other strand. This is illustrated in Figure 7.6. 

The size of the genomic DNA in eukaryotic cells (such as the cells of yeast, plants, or mammals) is much larger (up to 10+11 base pairs) than in E. coli (ca. 10+6 base pairs). The rate of the eukaryotic replication fork movement is about fifty nucleotides per second, which is about ten times slower than in E. coli. To complete replication in the relatively short time periods observed, multiple origins of replication are used. In yeast cells, these multiple origins of replication are called autonomous replication sequences (ARSs). As with prokaryotic cells, eukaryotic cells have multiple DNA polymerases. DNA polymerase S, complexed with a protein called proliferating... 

Second, common sense should be applied in choosing which specimens to use to generate replicate sequences of alleles identified as identical by DGGE. For example, specimens representing the extremes of the observed geographic distribution of the alleles might be chosen. 

Most progress in understanding this has been made in the yeast Saccharomyces cerevisiae from the chromosomes of which sequences have been identified that allow initiation of replication when inserted into plasmids (see below). These sequences are called autonomously replicating sequences (ARSs). It is likely that some of them, at least, represent bona fide replication origins. Presumably the mechanism of initiation at these origins is similar to that which has been elucidated in bacteria. 

ARS Automatic replicating sequence or autonomously replicating sequence... 

The answer is c. (Murray, pp 412-434. Scriver, pp 3-45. Sack, pp 3—29. Wilson, pp 99-121.) Despite the great length of the chromosomes of eukaryotic DNA, the actual replication time is only minutes. This is because eukaryotic DNA is replicated bidirectionally from many points of origin. The hundreds of initiation sites for DNA replication on chromosomes share a consensus sequence called an autonomous replication sequence (ARS). Thus, while the process of DNA replication in mammals is similar to that in bacteria, with DNA polymerases of similar optimal temperatures and speed, the many replication forks allow for a rapid synthesis of chromosomal DNA. Proteins such as histones, which are bound to mammalian chromosomes, inhibit DNA replication or transcription. Dissociation of the protein-DNA complex (chromatin) and unwinding of DNA supercoils (followed by chromatin reassembly) is part of the replication process. 

As discussed In Chapter 4, replication of DNA begins from sites that are scattered throughout eukaryotic chromosomes. The yeast genome contains many 100-bp sequences, called autonomously replicating sequences (ARSs), that act as replication origins. The observation that Insertion of an ARS into a circular plasmid allows the plasmid to replicate In yeast cells provided the first functional Identification of origin sequences in eukaryotic DNA (see Figure 10-32a). 

Table 7-12 lists the various sites in the complex viral replication sequence where selective intervention with drugs is theoretically possible. Inhibition of mRNA processing as part of ribavirin s mechanism has been proposed. One other potential area that has only begun to be explored is in the final assembly steps, where the newly synthesized viral nucleic acids and structural proteins come together on newly formed membranes. Inhibition of such viral membranes thus becomes a viable chemotherapeutic approach. 

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