DNA polymerase families

Fig. 2. Structures of family A, B, X, Y, and RT polymerases. The proteins are in ribbon representation. The fingers, palm, and thumb subdomains are color-coded in gold, red, and green, respectively. (A) Structure of apo Klentaql (family A). The 3 -5 vestigial exonuclease domain is indicated in silver. (B) Structure of apo RB69 DNA polymerase (family B). The 3 -5 exonuclease domain and the N-terminal domain are indicated in grey and silver, respectively. (C) Structure of apo pol / DNA polymerase (family X). The lyase domain is indicated grey. (D) Structure of the Dpo4 DNA polymerase (family Y). The litde finger subdomain is indicated in silver. (E) Structure of the p66 subunit of reverse transcriptase (RT family). The RNAseH and connection subdomains are indicated in grey and silver, respectively.

There are three main DNA polymerase families of interest to the modified nucleotide community Family A, Family B, and Family DNA polymerases with homology to the pro-... 

According to present views, all of the known DNA polymerases are divided into seven families based on their sequence homology (especially, sequences of the catalytic domain) and the stmcture of catalytic domain. Six of them—A, B, C, D, X and Y—are DNA-dependent DNA polymerases, one is a DNA polymerase of a different nature, namely it is RNA-dependent (more commonly known as reverse transcriptases or RT family) [3]. The spectra of DNA polymerases families are individual for different organic kingdoms. For example, bacteria usually contain DNA polymerases of A, B, C, X and Y families, while archaea have members of families B, D, X and Y. Among eukaryotic DNA polymerases, we can find various members of A, B, X, Y families (and at least one RT-member—telomerase supplying synthesis of the terminal fragment of chromosome which caimot be synthesized in the matrix way). Viral DNA polymerases are presented by families A, B and X (as well as RT—reverse transcriptases of retrovirases) (see Table 4.1). 

Fig. 4.2 Comparative fidelity of different DNA polymerase families. (Adapted with permission from [7])...

Yamtich J, Sweasy JB (2010) DNA polymerase family X function, structure, and cellular roles. Biochim Biophys Acta 1804(5) 1136-1150... 

The isolation from a marine ascidian and subsequent structure determination of polycitone A (105) (Fig. 6) was first reported [52] by Kashman and coworkers in 1994. In this paper, the penta-O-methyl derivative was reported to inhibit the growth of SV40 transformed fibroblast cells at a concentration of 10 jtg/mL. Loya, Hizi and Kashman published [53] an extensive account of the biological activity of polycitone A in 1999 in which case inhibition of retroviral reverse transcriptases and cellular DNA polymerases was described. The isolation from an ascidian and structure determination of polycitone B (106) (Fig. 4) was subsequently reported [54] by Kashman and coworkers in 2000. Obviously, the presence of extensive bromination in both polycitone A and B make this family of compounds unique among the 3,4-diarylpyrrole natural products. 

Mammals have many low-fidelity DNA polymerases of the TLS polymerase family. However, the presence of these enzymes does not necessarily translate into an unacceptable mutational burden, because most of the... 

Fig. 26-4A) synthesized DNA normally. This finding stimulated an intensive search for new polymerases. Two were found DNA polymerases II (gene pol B)264 and III. Both are present in amounts less than 25% of that of DNA polymerase I.265 266 Both have properties similar to those of polymerase I, but there are important differences. By now DNA polymerases have been isolated from many organisms, many genes have been cloned and many sequences, both of bacterial and eukaryotic polymerases are known. Comparisons of both sequences and three-dimensional structures,266a/b a few of which are shown in Fig. 27-12, suggest that the polymerases belong to at least six families (Table 27-1). These include the RNA-dependent DNA polymerases known as reverse transcriptases as well as some RNA polymerases.267 2681... 

This chapter will review the current understanding of the nucleotide incorporation cycle by DNA polymerases and the mechanisms employed by DNA polymerases to replicate DNA accurately. It includes a review of more recent and stimulating work that explores the mechanochemistry of DNA polymerases and their role as force generators and molecular motors. Although additional activities are present on many polymerases (e.g., 5 -3 exonuclease [family A], a 3 -5 exonuclease [family A and B],... 

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). 

Known members of the family X polymerases include eukaryotic DNA polymerase [1 (pol fi) (Abbotts et al., 1988), polymerase a (Burgers et al, 2001), polymerase fi (Dominguez et al, 2000), polymerase X (Garcia-Diaz et al, 2000), yeast polymerase IV (Prasad et al, 1993), and the African swine fever virus polymerase X (Martins et al, 1994). Pol [1 is known to be involved in the base excision repair (BER) pathway, which is important for repairing... 

The best characterized family X member is DNA pol [1, the smallest eukaryotic polymerase. Although family X polymerases seem to have evolved separately from other classes of DNA polymerases, they share... 

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