Thymine glycols and urea residues in M13 DNA constitute replicative blocks<i>in vitro</i>

Ide, Hiroshi; Kow, Yoke W.; Wallace, Susan S.

doi:10.1093/nar/13.22.8035

Cited by 262 publications

(203 citation statements)

References 31 publications

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“…If the conditions of synthesis were relaxed by substitution of manganese for magnesium ions in the reaction mixture, dAMP was incorporated opposite the lesions. This is consistent with previous reports that DNA polymerases introduce dAMP residues opposite any non-informative lesion (Strauss et al, 1982;Boiteux & Laval, 1982;Schaaper et al, 1983;Kunkel, 1984) but it could also be due to thymine glycol coding as thymine (Ide et al, 1985). The processivity was dependent on the presence of a pyrimidine preceding the thymine glycol.…”

Section: Dna Lesions and Their Repairsupporting

confidence: 92%

“…Several groups have now established that ring-saturated thymine lesions are non-coding rather than miscoding (Hariharan et al, 1977;Ide et al, 1985;Rouet & Essingmann, 1985;Clark & Beardsley, 1986;Hayes & Le Clerk, 1986). DNA templates have been oxidized to yield thymine glycols or further, unspecified, breakdown products (possibly urea).…”

Section: Dna Lesions and Their Repairmentioning

confidence: 99%

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Ionizing radiation-induced mutagenesis

Breimer

1988

Br J Cancer

149

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Section: Dna Lesions and Their Repairsupporting

confidence: 92%

Section: Dna Lesions and Their Repairmentioning

confidence: 99%

Ionizing radiation-induced mutagenesis

Breimer

1988

Br J Cancer

149

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“…Thus, there may be as many as three routes to thymine glycol repair: endo III; exonuclease III and endo IV; and SOS (13). These results indicate that thymine glycol sites can be repaired in vivo in organisms ranging from E. coli to mammals.The presence of thymine glycol in DNA can have profound consequences on DNA replication (9,13,(23)(24)(25)(26)(27). The presence of thymine glycol is a block to replication (23-28).…”

mentioning

confidence: 99%

“…The presence of thymine glycol in DNA can have profound consequences on DNA replication (9,13,(23)(24)(25)(26)(27). The presence of thymine glycol is a block to replication (23)(24)(25)(26)(27)(28).…”

mentioning

confidence: 99%

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Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

Kung

Bolton

1997

Journal of Biological Chemistry

105

114

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Oxidative stress, ionizing radiation, and other events can induce the oxidation of the thymine in DNA to thymine glycol. The presence of thymine glycol can have significant biological consequences, and there are specific repair enzymes for thymine glycol in a wide range of organisms. The structure of a duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine) has been determined by the combined use of NMR and restrained molecular dynamics. The duplex of d(C 1 G 2 C 3 G 4 A 5 Tg 6 A 7 C 8 G 9 C 10 C 11 ) paired with d(G 22 C 21 G 20 -C 19 T 18 A 17 T 16 G 15 C 14 G 13 G 12 ), with Tg indicating thymine glycol, has been used for these studies. The structure shows that the thymine glycol induces a significant, localized structural change with the thymine glycol largely extrahelical. This structural information is consistent with the biological consequences of thymine glycol in DNA. This structure is compared with that of a DNA duplex with an abasic site in the same sequence context.Damage to DNA can occur by the spontaneous deamination of cytosine to uracil and through the action of alkylating agents, oxidants, drugs, and toxins, ionizing radiation, and other modes of action (1-3). The exposure of DNA in cells bound to proteins as a solid or free in solution to ionizing radiation or to oxidative stress can lead to the conversion of thymine to thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine). Approximately 10 -20% of the damage to DNA induced by ionizing radiation, including that used to treat tumors, is the result of thymine base oxidation and fragmentation. These products can also be produced by oxidative stress. In addition, the importance of damaged DNA as a control on the cell cycle is increasingly becoming a focus of research efforts so that the effects of damaged thymines on the structures, stabilities, dynamics, and interactions of DNA are of interest.It has been known for several decades that ionizing radiation can stop the reproduction of cells as well as kill cells. These activities form the basis for using radiation in chemotherapy, and the research in this area has been frequently reviewed (1-13). Since the mid-1950s there have been studies on the effects of ionizing radiation on the chemical integrity of DNA (4,5,7,9, 14). Ionizing radiation can induce a number of types of damage to DNA including single and double strand breaks, oxidation of the purine and pyrimidine bases, and cross-linking of DNA with proteins. Radiation-generated oxidants are thought to react with thymine to lead to the formation of thymine glycol, thymine peroxide, thymine hydroperoxide, and other oxidized forms of the base. Some of these oxidized forms of thymine subsequently react further to form urea. Some of the same types of damage also occurs to DNA during oxidative stress (5,15,16).The damage to the thymine bases in DNA is of special interest because the major forms of damaged thymine are known; thymine is the most easily oxidized base, and many of the biological consequences of damaged thymines a...

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DNA base damage induced by ionizing radiation recognized byEscherichia coli UvrABC nuclease but not Nth or Fpg proteins

Roldán-Arjona¹,

Sedgwick²

1996

Mol. Carcinog.

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Ionizing radiation and other free radical-generating systems induce a great variety of oxidative damage to DNA bases. The major known lesions are repaired by two well-characterized DNA glycosylases of Escherichia coli, endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), which have associated AP lyase activities. To detect and characterize potentially harmful oxidative base DNA lesions that may be repaired by alternative means, we exposed plasmid DNA to low doses of gamma-rays and removed the major base lesions by treatment with Nth and Fpg proteins. The closed circular DNA remaining after these treatments was used as a substrate of the UvrABC endonuclease complex from E. coli and as a template in a DNA polymerase arrest assay in vitro. The circular DNA contained lesions that were recognized and incised by the UvrABC nuclease and also lesions that blocked DNA polymerization in vitro. The blocking lesions were more abundant in DNA irradiated under nitrogen than under air and occurred mainly at tandem guanines; however, they were also frequent at tandem adenines and tandem cytosines.

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Thymine glycols and urea residues in M13 DNA constitute replicative blocksin vitro

Cited by 262 publications

References 31 publications

Ionizing radiation-induced mutagenesis

Ionizing radiation-induced mutagenesis

Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

DNA base damage induced by ionizing radiation recognized byEscherichia coli UvrABC nuclease but not Nth or Fpg proteins

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