Replication polymerase

Bacterial family C polymerases are the major chromosomal replicative enzyme (Kornberg and Baker, 1992). Like other replicative polymerases, the holoenzyme interacts with other proteins and forms a large multisubunit complex consisting of at least 10 subunits (Kornberg and Baker, 1992). The a-subunit contains the DNA polymerase activity that is tightly associated with the e-subunit, which contains a 3 -5 exonuclease activity (Kelman and O Donnell, 1995). 

HIV-1 RT has an extremely low discrimination at Step 3, varying between 7- and 90-fold (Kati et al, 1992). This low discrimination at Step 3 results in HIV-1 RT having one of the lowest fidelities among replicative polymerases. The level of discrimination against incorrect nucleotides by HIV-1 RT is lower even than family Y polymerases, for example, yeast pol rj, which... 

Kim S, Dallmann HG, McHenry CS, Marians KJ. Coupling of 62. a replicative polymerase and helicase a tau-DnaB interaction mediates rapid replication fork movement. Cell 1996 84 643-650. 

Polymerase I plays an essential role in the replication process in E. coli, but it is not responsible for the overall polymerization of the replicating strands. The enzyme that accomplishes this is a less abundant enzyme, polymerase III (pol III). (A DNA polymerase II has also been isolated from E. coli, but it probably plays no role in DNA synthesis.) Pol III catalyzes the same polymerization reaction as pot I but has certain distinguishing features. It is a very complex enzyme and is associated with eight other proteins to form the pol III holoenzyme. (The term holoenzyme refers to an enzyme that contains several different subunits and retains some activity even when one or more subunits is missing.) Pol III is similar to pol I in that it has a requirement for a template and a primer but its substrate specificity is much more limited. For a template pol III cannot act at a nick nor can it unwind a helix and carry out strand displacement. The latter deficiency means that an auxiliary system is needed to unwind the helix ahead of a replication fork. Pol III, like pol I, possesses a 3 5 exonuclease activity, which performs the major editing function in DNA replication. Polymerase III also has a y exonuclease activity, but this activity does not seem to play a role in replication. 

Tujo distinct polymerases are needed to copy a eukaryotic replicon. An initiator polymerase called polymerase a begins replication but is soon replaced by a more processive enzyme. This process is called polymerase switching because one polymerase has replaced another. This second enzyme, called DNA polymerase 5, is the principal replicative polymerase in eukaryotes (Table 28.2). 

A variety of mechanisms have evol ved to deal with such interruptions, including specialized DNA polymerases that can replicate DNA across many lesions. A drawback is that such polymerases are substantially more error prone than are normal replicative polymerases. Nonetheless, these error-pToiie... 

Figure 13.4 Polymerase bypass of bulky lesions, (a) Chemical structure of B[o]P-dC. The dNTP binding site (yellow circle) of the model replicative polymerase BF is blocked by the B[fl]P-dC adduct (red circle, labeled [BPJdC) (PDB 1XC9). Dpo4 can flip the B[o] P-dC adduct (red circle) out of the polymerase active site, which allows the incoming dNTP to bind (PDB 2IA6). (b) Y-family...

Stukenberg P. T., Turner J., O Donnell M. (1994) An explanation for lagging strand replication Polymerase hopping among DNA sliding clamps. Cell 78 877. 

The major . ro/2 replicative polymerase Pol III belongs to Family C (for review see Kelman and O Donnell" and O Donnell et al ). The D Family is found only in archaebacteria, and includes Pyrococcus furiosus Pfu) Pol D." ... 

When a replicative polymerase encounters a thymine dimer, it cannot replicate past the site. Deoxyadenylate can be incorporated opposite the first thymine base in the template, but the double helix distortion induced by the thymine dimer, causes the structure to be recognized as a mismatch, and the polymerase "idles" at the damage site, converting dATP to dAMP by a continual process of insertion and exonucleolytic cleavage (due to proofreading). 

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