AP lyases and dRPases: commonality of mechanism

Piersen, C E; McCullough, Amanda K.; Lloyd, R. Stephen

doi:10.1016/s0921-8777(99)00054-3

Cited by 98 publications

(81 citation statements)

References 35 publications

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“…Some DNA glycosylases also display a class I AP lyase activity that incises the phosphodiester linkage on the 3' side of the AP lesion and generates a 5'-phosphate group and a 3'-terminus that needs removal by a class II AP endonuclease/3'-diesterase prior to repair synthesis and ligation (Piersen et al, 2000). The cleavage of AP sites can also be catalyzed by class II AP endonucleases which incise the 5' side of the AP site, leaving a 3'-OH terminus and a 5'-abasic residue that is removed by a deoxyribophosphodiesterase (dRPase) (Mol et al, 2000).…”

Section: Dna Repair Pathways and Antioxidant Defense Systems Base Excmentioning

confidence: 99%

Several pathways of hydrogen peroxide action that damage the E. coli genome

Asad

Almeida

et al. 2004

Genet. Mol. Biol.

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Hydrogen peroxide is an important reactive oxygen species (ROS) that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER), nucleotide excision repair (NER) and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm) and H 2 O 2 , the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H 2 O 2 under low-iron conditions. Key words: hydrogen peroxide, cross-adaptive response, lethal synergism, copper and iron. General AspectsThe appearance of aerobic forms of life was an important step in the evolutionary process, since oxygen consumption leads to the production of ten-fold more energy from glucose than does anaerobic metabolism (Meneghini, 1987). However, this process imposes constraints on cell viability, because of the generation of reactive oxygen species during respiration.The consecutive univalent reduction of molecular oxygen to water produces three active intermediates: superoxide anion (O 2 -• ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH • ). These intermediates, collectively referred to as reactive oxygen species (ROS) are potent oxidants of lipids, proteins, and nucleic acids (Halliwell and Gutteridge, 1984;Mello-Filho and Meneghini, 1985;Meneghini, 1988). Among the oxidative DNA lesions, one of the major classes of DNA damage leads to modification in purine and pyrimidine bases, together with oligonucleotide strand breaks, DNA-protein cross-links and abasic sites. Increasing evidence suggests that the cumulative damage caused by ROS contributes to numerous degenerative diseases associated with aging, such as atherosclerosis, rheumatoid arthritis and cancer (Ames et al., 1993;Halliwell and Gutteridge, 1999).Living organisms have developed specific mechanisms to prevent the production and effects of ROS. The reduction of O 2 by cytochrome oxidase without yielding ROS, the superoxide dismutase catalysis of O 2 -• into H 2 O 2 through a dismutation reaction, the decomposition of H 2 O 2 by catalase and peroxidases, and the scavenging of ROS by some vitamins comprise part of the set of cellular antioxidant defenses (Halliwell and Gutteridge, 1999). Synthesis of the enzymes that catalyze these reactions is a part of the adaptive response tr...

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Section: Dna Repair Pathways and Antioxidant Defense Systems Base Excmentioning

confidence: 99%

Several pathways of hydrogen peroxide action that damage the E. coli genome

Asad

Almeida

et al. 2004

Genet. Mol. Biol.

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“…Following uracil excision, the resultant baseless site can be cleaved by a class II apurinic/ apyrimidinic (AP) endonuclease to generate a terminal 3′-hydroxyl and a deoxyribose 5′-phosphate (dRP) residue [18]. The dRP residue, together with one or more nucleotides, may be removed by the 5′-3′-exonuclease activity of DNA polymerase I (Pol I) [19] or by the deoxyribophosphodiesterase (dRPase) activity of Fpg protein [20]. A DNA repair patch, characterized as short (one nucleotide) or long (>1 nucleotide) is synthesized by DNA Pol I, and NAD + -dependent DNA ligase (Lig) catalyzes phosphodiester bond formation to seal the DNA chain [21].…”

Section: Introductionmentioning

confidence: 99%

Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance

et al. 2006

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The steady-state levels of uracil residues in DNA extracted from strains of Escherichia coli were measured and the influence of defects in the genes for uracil-DNA glycosylase (ung), doublestrand uracil-DNA glycosylase (dug), and dUTP pyrophosphatase (dut) on uracil accumulation was determined. A sensitive method, called the Ung-ARP assay, was developed that utilized E. coli Ung, T4pdg, and the Aldehyde Reactive Probe reagent to label a basic sites resulting from uracil excision with biotin. The limit of detection was one uracil residue per million DNA nucleotides (U/10 6 nt). Uracil levels in the genomic DNA of E. coli JM105 (ung + dug + ) were at the limit of detection, as were those of an isogenic dug mutant, regardless of growth phase. Inactivation of ung in JM105 resulted in 31 ± 2.6 U/10 6 nt during early log growth and 19 ± 1.7 U/ 10 6 nt in saturated phase. An ung dug double mutant (CY11) accumulated 33 ± 2.9 U/10 6 nt and 23 ± 1.8 U/10 6 nt during early log and saturated phase growth, respectively. When cultures of CY11 were supplemented with 20 ng/ml of 5-fluoro-2′-deoxyuridine, uracil levels in early log phase growth DNA rose to 125 ± 1.7 U/10 6 nt. Deoxyuridine supplementation reduced the amount of uracil in CY11 DNA, but uridine did not. Levels of uracil in DNA extracted from CJ236 (dut-1 ung-1) were determined to be 3000-8000 U/10 6 nt as measured by the Ung-ARP assay, twodimensional thin-layer chromatography of metabolically-labeled 32 P DNA, and LC/MS of uracil and thymine deoxynucleosides. DNA sequencing revealed that the sole molecular defect in the CJ236 dUTP pyrophosphatase gene was a C→T transition mutation that resulted in a Thr24Ile amino acid change.

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“…The extensive 5Ј-resection that occurs in the first steps of recombination also likely removes blocking lesions at double-strand breaks (7,8). Common blocking lesions on 3Ј termini include phosphates, ␣,␤-unsaturated aldehydes resulting from ␤-elimination reactions (9), and phosphoglycolate moieties that are the primary product of bleomycin action (10). The most potent 3Ј-processing enzymes are the apurinic-apyrimidinic endonucleases, which, in addition to cleaving strands at abasic sites, possess 3Ј-diesterase activities capable of removing most nucleotide fragments (11)(12)(13).…”

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confidence: 99%

Uncoupling of 3′-Phosphatase and 5′-Kinase Functions in Budding Yeast

Vance

Wilson

2001

Journal of Biological Chemistry

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Polynucleotide kinase is a bifunctional enzyme containing both DNA 3-phosphatase and 5-kinase activities seemingly suited to the coupled repair of singlestrand nicks in which the phosphate has remained with the 3-base. We show that the yeast Saccharomyces cerevisiae is able to repair transformed dephosphorylated linear plasmids by non-homologous end joining with considerable efficiency independently of the end-processing polymerase Pol4p. Homology searches and biochemical assays did not reveal a 5-kinase that would account for this repair, however. Instead, open reading frame YMR156C (here named TPP1) is shown to encode only a polynucleotide kinase-type 3-phosphatase. Tpp1p bears extensive similarity to the ancient L-2-haloacid dehalogenase and DDDD phosphohydrolase superfamilies, but is specific for double-stranded DNA. It is present at high levels in cell extracts in a functional form and so does not represent a pseudogene. Moreover, the phosphatase-only nature of this gene is shared by Saccharomyces mikatae YMR156C and Arabidopsis thaliana K15M2.3. Repair of 3-phosphate and 5-hydroxyl lesions is thus uncoupled in budding yeast as compared with metazoans. Repair of transformed dephosphorylated plasmids, and 5-hydroxyl blocking lesions more generally, likely proceeds by a cycle of base removal and resynthesis.Oxidative damage to DNA can result from endogenously generated reactive oxygen species or from exposure to exogenous agents such as ionizing radiation or anticancer agents such as bleomycin and neocarzinostatin (reviewed in Ref. 1). Such damage and the enzymes involved in its repair frequently produce fragmentation of the deoxyribose sugar backbone, resulting in DNA strand breaks bearing abnormal structures at the 3Ј and 5Ј termini. These are termed "blocking lesions" because they prevent the reactions necessary to achieve final repair of the damaged strand, namely polymerization and ligation. Since both single-and double-strand lesions can occur with potential consequences that include replication failure and genomic rearrangement, the resolution of blocking lesions is of major importance in genome maintenance. Although many chemical forms are possible, important blocking lesions on 5Ј termini include hydroxyls and deoxyribose phosphates. As an example of the redundancies in end processing, deoxyribose phosphate moieties can be removed in short-patch base excision repair (BER) 1 by the lyase function of DNA polymerase ␤ (2, 3) or certain glycosylases (4, 5) or in long-patch BER by flap excision and resynthesis (6). The extensive 5Ј-resection that occurs in the first steps of recombination also likely removes blocking lesions at double-strand breaks (7,8). Common blocking lesions on 3Ј termini include phosphates, ␣,␤-unsaturated aldehydes resulting from ␤-elimination reactions (9), and phosphoglycolate moieties that are the primary product of bleomycin action (10). The most potent 3Ј-processing enzymes are the apurinic-apyrimidinic endonucleases, which, in addition to cleaving strands at abasic sites, po...

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AP lyases and dRPases: commonality of mechanism

Cited by 98 publications

References 35 publications

Several pathways of hydrogen peroxide action that damage the E. coli genome

Several pathways of hydrogen peroxide action that damage the E. coli genome

Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance

Uncoupling of 3′-Phosphatase and 5′-Kinase Functions in Budding Yeast

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