HMB 205 notes - Initiation of genome replication Each virus genome has a specific sequence where nucleic acid replication is initiated This sequence is

HMB 205 notes - Initiation of genome replication Each virus...

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Initiation of genome replication Each virus genome has a specific sequence where nucleic acid replication is initiated. This sequence is recognized by the proteins that initiate replication. Nucleic acid replication requires priming, which is the first reaction of a nucleotide with an –OH group on a molecule at the initiation site. Replication of the genomes of many RNA viruses (including rotaviruses, and rhabdoviruses) initiates when the first nucleotide of the new strand base pairs with a nucleotide in the viral RNA. The initial nucleotide effectively acts as a primer for RNA replication when its 3_ –OH group becomes linked to the second nucleotide. Some ssDNA viruses, such as parvoviruses, use self- priming. At the 3_ end of the DNA there are regions with complementary sequences that can base pair. The –OH group of the nucleotide at the 3_ end forms a linkage with the first nucleotide, and then DNA synthesis proceeds by a rather complex process to ensure that the whole genome is copied. In order to initiate the replication of many DNA genomes, and some RNA genomes, a molecule of RNA or protein is required to act as a primer. RNA and protein primers Synthesis of cell DNA commences after a region of the double helix has been unwound by a helicase and after a primase has synthesized short sequences of RNA complementary to regions of the DNA. These RNAs act as primers; one is required for the leading strand, while multiple primers must be synthesized for the Okazaki fragments of the lagging strand. The first nucleotide of a new sequence of DNA is linked to the 3_ –OH group of the primer RNA. Some DNA viruses also use RNA primers during the replication of their genomes. Some viruses, such as polyomaviruses, use the cell primase to synthesize their RNA primers, while others, such as herpesviruses and phage T7, encode their own primases. During their replication cycle the retroviruses synthesize DNA from a (+) RNA template. They use a cell transfer RNA to prime (−) DNA synthesis. The retrovirus DNA becomes integrated into a cell chromosome. If the infection is latent and the cell subsequently divides, then the virus DNA is copied along with the cell DNA, using RNA primers synthesized by the cell primase. For some viruses the primer for initiation of nucleic acid replication is the –OH group on a serine or tyrosine residue in a protein. DNA viruses that use protein primers include some animal viruses (e.g. adenoviruses) and some phages (e.g. tectiviruses). RNA viruses that use protein primers include some animal viruses (e.g. picornaviruses) and some plant viruses (e.g. luteoviruses).
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Hepadnaviruses are DNA viruses that use a protein primer to initiate (−) DNA synthesis and an RNA primer to initiate (+) DNA synthesis. Protein primers (and the RNA primers of hepadnaviruses) are not removed once their role is performed and they are found linked to the 5_ ends of the genomes in virions.
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