Although smoking is a major cause of lung cancer, only proportion smokers develop suggesting genetic predisposition in some individuals. Because tobacco associated with the increased formation DNA lesions, including those induced from oxidative damage, we investigated whether activity repair enzyme 8-oxoguanine N-glycosylase (OGG), which repairs lesion 8-oxoguanine, cancer.We conducted molecular epidemiologic case-control study that included 68 case patients non-small-cell cancer and healthy...

The unique properties of DNA make it a fundamental building block in the fields supramolecular chemistry, nanotechnology, nano-circuits, molecular switches, devices, and computing. In our recently introduced autonomous automaton, molecules serve as input, output, software, hardware consists restriction ligation enzymes using ATP fuel. addition to information, stores energy, available on hybridization complementary strands or hydrolysis its phosphodiester backbone. Here we show that single...

Abstract An increasing number of studies indicate that reduced DNA-repair capacity is associated with increased cancer risk. Using a functional assay for the removal oxidative DNA lesion 8-oxoguanine by enzyme glycosylase 1 (OGG1), we have previously shown OGG activity risk factor in lung cancer. Here, report peripheral blood mononuclear cells from 37 cases squamous cell carcinoma head and neck (SCCHN) was significantly lower than 93 control subjects, frequency matched age gender. Retesting...

Purpose: To measure the yield of DNA strand breaks and clustered lesions in plasmid irradiated with protons, helium nuclei, γ-rays.Materials methods: Plasmid was 1.03, 19.3 249 MeV protons (linear energy transfer = 25.5, 2.7, 0.39 keV μm – 1 respectively), 26 nuclei (25.5 μm) γ-rays (137Cs or 60Co) phosphate buffer containing 2 mM 200 glycerol. Single-and double-strand (SSB DSB) were measured by gel electrophoresis, base quantified converting them into irreparable DSB transformed...

Only a minority of smokers develop lung cancer, possibly due to genetic predisposition, including DNA repair deficiencies. To examine whether inter-individual variations in activity N-methylpurine glycosylase (MPG) are associated with we conducted blinded, population-based, case–control study 100 cancer case patients and matched control subjects analyzed the data conditional logistic regression. All statistical tests were two-sided. MPG enzyme peripheral blood mononuclear cells from was...

DNA repair is a prime mechanism for preventing damage, mutation, and cancers. Adopting functional approach, we examined the association with lung cancer risk of an integrated score, measured by panel three enzymatic activities in peripheral blood mononuclear cells. The included assays AP endonuclease 1 (APE1), 8-oxoguanine glycosylase (OGG1), methylpurine (MPG), all which oxidative damage as part base excision pathways. A blinded population-based case-control study was conducted 96 patients...

The key role of DNA repair in removing damage and minimizing mutations makes it an attractive target for cancer risk assessment prevention. Here we describe the development a robust assay apurinic/apyrimidinic (AP) endonuclease 1 (APE1; APEX1), essential enzyme involved oxidative damage. APE1 enzymatic activity was measured peripheral blood mononuclear cell protein extracts using radioactivity-based assay, its association with lung determined conditional logistic regression specimens from...

Abstract DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of containing known lesion, measures the division labor between two DDT pathways. We show that in absence damage response, most common sunlight-induced TT-CPD, achieved by TLS mouse embryo...

Bypass synthesis by DNA polymerase II was studied using a synthetic 40-nucleotide-long gapped duplex containing site-specific abasic site analog, as model system for mutagenesis associated with lesions. involved rapid polymerization step terminating opposite the nucleotide preceding lesion, followed slow bypass step. found to be dependent on and dNTP concentrations, sequence context, size of gap. A side-by-side comparison polymerases I, II, III core revealed following. 1) Each three bypassed...

Bypass synthesis by DNA polymerase I was studied using synthetic 40-nucleotide-long gapped duplex DNAs each containing a site-specific abasic site analog, as model system for mutagenesis associated with lesions. proceeded in two general stages: fast polymerization stage that terminated opposite the followed slow bypass and down to end of template. The position 3'-terminus primer relative analog did not affect range −1 −5. In contrast, increased distance 5'-boundary gap from lesion up 3-fold...

DNA repair is a major mechanism for minimizing mutations and reducing cancer risk. Here, we present the development of reproducible specific enzymatic assays methylpurine glycosylase (MPG) repairing oxidative lesions 1,N6-ethenoadenine (εA) hypoxanthine (Hx) in peripheral blood mononuclear cells protein extracts. Association these activities with lung was determined using conditional logistic regression specimens from population-based case–control study 96 cases matched control subjects. The...

Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we relationship between level repair global gene expression.

TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little known. Here, we show that regulates multiple biological pathways and focuses on its multilayer regulation translesion DNA synthesis (TLS), in error-prone polymerases bypass unrepaired lesions. We mRNA stability and/or translation polymerase η RAD18 E3 ligase, guides the to replication stalling sites monoubiquitinates PCNA, thereby enabling recruitment damaged sites. Remarkably, addition effect via controlling tail,...

The β subunit of DNA polymerase III holoenzyme Escherichia coli is a 40.6-kDa protein that functions as sliding clamp (Stukenberg, P. T., Studwell-Vaughan, S., and O'Donnell, M.(1991) J. Biol. Chem. 266, 11328-11334). It responsible for tethering the to endowing it with high processivity required replication. Here in companion study (Paz-Elizur, Skaliter, R., Blumenstein, Livneh, Z.(1996) 271, 2482-2490) we report dnaN gene, encoding subunit, contains an internal in-frame termed dnaN*,...

The 40.6-kDa β subunit of DNA polymerase III Escherichia coli is a sliding clamp responsible for tethering the to and endowing it with high processivity (Stukenberg, P. T., Studwell-Vaughan, S., O'Donnell, M.(1991) J. Biol. Chem. 266, 11328-11334). UV irradiation E. induces smaller 26-kDa form subunit, termed β*, that, when overproduced from plasmid, increases resistance (Skaliter, R., Paz-Elizur, Livneh, Z.(1996) 271, 2478-2481). Here we show that this protein synthesized UV-inducible...

DNA lesions that block replication can be bypassed in Escherichia coli by a special synthesis process termed translesion replication. This is mutagenic due to the miscoding nature of lesions. We report repair enzyme formamido-pyrimidine glycosylase and general damage recognition protein UvrA each inhibit specifically through an abasic site analog purified polymerases I II, polymerase III (α subunit) from E. coli.In vivo experiments suggest similar inhibitory mechanism prevents at least 70%...