Disease relevance of POLQ

• It is an A-family DNA polymerase related to Escherichia coli pol I, human POLQ, and Drosophila Mus308 [1].
• Full-length human POLQ was expressed from a baculovirus system [2].
• Lack of DNA polymerase eta and the attendant defect in bypass replication of pyrimidine dimers induced in DNA by ultraviolet light (UV) underlie the enhanced mutagenesis and carcinogenesis observed in xeroderma pigmentosum variant (XP-V) [3].
• Adenovirus mediated transduction of the human DNA polymerase eta cDNA [4].
• In addition to this, significant new information has become available on how B cell activation-associated DNA-modifying events, involving activation-induced cytidine deaminase and DNA polymerase-eta, contribute to the molecular lesions that result in AIDS-associated lymphoma [5].

High impact information on POLQ

• The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation [6].
• POLQ has three sequence insertions between conserved motifs in its catalytic site [7].
• The proteins encoded by the XPA, -B, -C, -D, -F, and -G genes are required for nucleotide excision repair, and the XPV gene encodes DNA polymerase eta, which carries out translesion DNA synthesis [8].
• The role of DNA polymerase eta in translesion synthesis past platinum-DNA adducts in human fibroblasts [9].
• Biochemical basis of genotoxicity of heterocyclic arylamine food mutagens: Human DNA polymerase eta selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site [10].

Chemical compound and disease context of POLQ

• PCR amplification of the highly conserved baculovirus genes late expression factor 8 (lef-8), late expression factor 9 (lef-9) and polyhedrin/granulin (polh/gran) combined with molecular phylogenetic analyses provide a powerful tool to identify lepidopteran-specific baculoviruses and to study their diversity [11].

Biological context of POLQ

• These results are consistent with a requirement for functional DNA polymerase eta in the replication of a double-stranded plasmid containing either a (6-4) photoproduct or a CPD, on the leading but not the lagging strand [12].
• UV-induced RPA phosphorylation is increased in the absence of DNA polymerase eta and requires DNA-PK [13].

Anatomical context of POLQ

• Immunoblotting with POLQ antibodies detected a protein of >250 kDa in extracts from HeLa cells [2].
• DNA polymerase theta is preferentially expressed in lymphoid tissues and upregulated in human cancers [14].
• Deficiency of the Caenorhabditis elegans DNA polymerase eta homologue increases sensitivity to UV radiation during germ-line development [15].

Associations of POLQ with chemical compounds

• Error-prone translesion synthesis by human DNA polymerase eta on DNA-containing deoxyadenosine adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [16].
• Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase eta [17].
• The N2-ethylguanine and the O6-ethyl- and O6-methylguanine lesions in DNA: contrasting responses from the "bypass" DNA polymerase eta and the replicative DNA polymerase alpha [18].
• Translesion synthesis by human DNA polymerase eta across oxidative products of guanine [19].
• Thymine-thymine CPDs, and probably also CPDs containing cytosine, are replicated in vivo in a largely accurate manner by a DNA polymerase eta (Pol eta) dependent process [20].

Other interactions of POLQ

• Biochemical characterization and immunoblot analysis allowed its identification as the human homologue of DNA polymerase theta (hpol theta), whose cDNA has been cloned by homology with the mus308 gene of Drosophila melanogaster but still awaited detailed biochemical characterization [21].
• DNA polymerase theta (Pol theta) is a recently identified family A polymerase that contains an intrinsic helicase domain [14].

Analytical, diagnostic and therapeutic context of POLQ

• Twenty-four hours after infection, the DNA polymerase eta-EGFP fusion protein was detected by Western blot analysis, demonstrating successful transduction by the adenoviral vector [4].

References