Disease relevance of POLS

• Although hepadnavirus replication occurs inside viral nucleocapsids, or cores, biochemical systems for analyzing this reaction are currently limited to unencapsidated Pols expressed in heterologous systems [1].
• Adenovirus (Ad) DNA polymerase (pol) belongs to the distinct subclass of the polalpha family of DNA pols that employs the precursor terminal protein (pTP) as primer [2].
• dnaE, the gene encoding one of the two replication-specific DNA polymerases (Pols) of low-GC-content gram-positive bacteria (E. Dervyn et al., Science 294:1716-1719, 2001; R. Inoue et al., Mol. Genet. Genomics 266:564-571, 2001), was cloned from Bacillus subtilis, a model low-GC gram-positive organism [3].
• Polk reviews prevention of wound infections [4].

High impact information on POLS

• DNA polymerases (pols) alpha, beta, gamma, delta, and epsilon are the key enzymes required to maintain the integrity of the genome under all these circumstances [5].
• Here we report that TRF4, an evolutionarily conserved gene necessary for chromosome segregation, encodes a DNA polymerase with beta-polymerase-like properties [6].
• Interestingly, when filling in a 1 base-pair gap, DNA synthesis and subsequent strand displacement was greatest in the presence of both pols iota and eta [7].
• Induction of pols eta and zeta occur with T cells, IgM crosslinking, or both stimuli [8].
• Previously, we have shown that proficient replication through the gamma-HOPdG adduct can be mediated by the sequential action of human DNA polymerases (Pols) iota and kappa, in which Poliota incorporates either pyrimidine opposite gamma-HOPdG, but Polkappa extends only from the cytosine [9].

Biological context of POLS

• The hTRF4-1 gene maps to chromosome 5p15, a region of frequent copy number alteration in several tumor types [10].
• The efficiency and fidelity of nucleotide incorporation by high-fidelity replicative DNA polymerases (Pols) are governed by the geometric constraints imposed upon the nascent base pair by the active site [11].
• Mammalian DNA polymerase kappa (pol kappa), a member of the UmuC/DinB nucleotidyl transferase superfamily, has been implicated in spontaneous mutagenesis [12].
• In both cell lines, cEPA arrested in the G1 phase, and increased cyclin E protein levels, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos [13].
• Conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols) and human DNA topoisomerases (topos). cEPA inhibited the cell growth of two human leukemia cell lines, NALM-6, which is a p53-wild type, and HL-60, which is a p53-null mutant, with LD50 values of 37.5 and 12.5 microM, respectively [13].

Anatomical context of POLS

• LAK1 is expressed without any structural modification, even on the surface of endothelial cells [14].
• Moreover, all CD16+ and CD56 (NKH1)+ lymphocytes coexpressed both LAK2 and LAK1 antigens [15].
• The relative proportions of DNA-polymerases alpha, beta, delta and epsilon (pols alpha, beta, delta and epsilon ) activities in isolated neuronal and astroglial cell fractions from developing, adult and aging rat brain cerebral cortex, were examined [16].
• Eukaryotic cells contain at least six different Pols, named alpha, beta, gamma, delta, epsilon, and zeta [17].
• More interestingly, LAK1 is shared by some other cell types, such as monocytes and vascular endothelial cells [18].

Associations of POLS with chemical compounds

• Translesion synthesis across bulky N2-alkyl guanine DNA adducts by human DNA polymerase kappa [19].
• Pol epsilon (as well as pols alpha and delta) is optimally active in 100-150 mM potassium glutamate and 15 mM MgCl2 [20].
• We reported previously that long chain unsaturated fatty acids such as polyunsaturated fatty acids (PUFA) (i.e., eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA)) inhibited the activities of eukaryotic pols in vitro [21].
• The inhibitory activities against DNA polymerases (pols) of catechin derivatives (i.e., flavan-3-ols) such as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, (+)-catechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-epigallocatechin gallate (EGCg) were investigated [22].
• In this paper, we present the first detailed biochemical investigation on the mechanism of action of resveratrol towards mammalian pols [23].

Other interactions of POLS

• We have isolated and sequenced two human TRF4 family members, hTRF4-1 and hTRF4-2 [10].
• Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene [12].

Analytical, diagnostic and therapeutic context of POLS

• In a case-control study, residents of Galion or Polk Township who had MS were compared to residents who did not have MS [24].
• Ultrastructural localization of the pols by immuno-electron microscopy revealed pol epsilon to localize predominantly to ring-shaped clusters at electron-dense regions of the nucleus, whereas pol delta was mainly dispersed on fibrous structures [25].

References