Mechanisms for Priming DNA Synthesis

DNA replication is a semiconservative process in which a DNA polymerase uses one DNA strand as a template for the synthesis of a second, complementary, DNA strand. However, in contrast to RNA polymerases, which can initiate RNA synthesis on a DNA template de novo, all DNA polymerases require a preexisting primer on which to initiate DNA synthesis (Kornberg and Baker 1992). One apparent exception to this rule is a mitochondria1 DNA (mtDNA)-encoded reverse transcriptase (RT) in Neurospora (Wang and Lambowitz 1993). Preexisting primers can be classified into four groups. The simplest primer consists of the 3'-hydroxyl (3'-OH) termini of DNA chains that are complementary to the DNA template and thereby form a stable duplex structure at the site where DNA synthesis begins. This primer is used for DNA repair (Friedberg and Wood, this volume), parvovirus DNA replication (Brush and Kelly; Cotmore and Tattersall; both this volume), some RTs. The second type of primer consists of a deoxyribonucleoside monophosphate that is covalently attached to a specific serine, threonine, or tyrosine residue of a protein. Examples are bacteriophage, plasmids, and animal viruses that replicate as a linear DNA genome, and animal viruses such as hepadnaviruses whose genome is partially doublestranded and partially single-stranded. The third type of primer consists of tRNA molecules that anneal to specific sequences in the RNA