8-OxoG retards the activity of the ligase III/XRCC1 complex during the repair of a single-strand break, when present within a clustered DNA damage site

Lomax, Martine E.; Cunniffe, Siobhan; O’Neill, Peter

doi:10.1016/j.dnarep.2003.11.006

Cited by 81 publications

(79 citation statements)

References 37 publications

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“…On the other hand, when peroxidation reactions are involved, as reported for 8-oxodGuo/dF (15), the incorporated atom comes from molecular oxygen due to addition of the pyrimidine peroxyl radical onto the C8 of the purine moiety (Scheme 1, path B). Therefore, to distinguish between the two mechanisms, we determined for both 8- 18 O-labeled atom (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

“…It is generally admitted that these damage sites could be produced in cellular DNA exposed to ionizing radiation as a consequence of several ionization events along the particle track (16). Removal of damage in LMDS has been shown to be less efficient than that of single lesions (17)(18)(19). Moreover, as a consequence of their repair, LMDS can induce highly genotoxic double-strand breaks (20,21).…”

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confidence: 99%

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HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Bergeron

Auvré

Radicella

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

123

113

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Reaction of HO• radicals with double-stranded calf thymus DNA produces high levels of and, to a minor extent, . Formation of the hydroxylated purine lesions is explained by addition of HO • to the C8 position of the purine moiety. It has been reported that tandem lesions containing a formylamine residue neighboring 8-oxodGuo could be produced through addition of a transiently generated pyrimidine peroxyl radical onto the C8 of an adjacent purine base. Formation of such tandem lesions accounted for ≈10% of the total 8-oxodGuo. In the present work we show that addition of HO • onto the C8 of purine accounts for only ∼5% of the generated 8-oxodGuo. About 50% of the 8-hydroxylated purine lesions, including 8-oxodGuo and 8-oxodAdo, are involved in tandem damage and are produced by peroxyl addition onto the C8 of a vicinal purine base. In addition, the remaining 45% of the 8-oxodGuo are produced by an electron transfer reaction, providing an explanation for the higher yield of formation of 8-oxodGuo compared to 8-oxodAdo. Interestingly, we show that >40% of the 8-oxodGuo involved in tandem lesions is refractory to excision by DNA glycosylases. Altogether our results demonstrate that, subsequently to a single oxidation event, peroxidation reactions significantly increase the yield of formation of hydroxylated purine modifications, generating a high proportion of tandem lesions partly refractory to base excision repair.DNA damage | DNA repair | peroxidation reaction | tandem lesions F ormation of oxidatively generated DNA lesions is associated with the occurrence of degenerative diseases, cancer, and aging (1). Therefore, reactions of reactive oxygen species, and among them the highly genotoxic hydroxyl radical (HO • ), with DNA constituents have been extensively studied during the last three decades (2). 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and, to a minor extent the corresponding adenine derivative 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxodAdo), have been shown to be significantly generated in cellular DNA under various conditions of oxidative stress. More than 20 years ago (3) it was established that in the presence of HO• (produced either by the indirect effect of ionizing radiation or by Fenton-type reactions) the mechanism of formation of 8-hydroxylated purine lesions (8-oxoPur), including both 8-oxodGuo and 8-oxodAdo, involves addition of HO• to the C8 position of the purine bases, followed by an oxidation reaction (for a review see refs. 2 and 4). In addition, 8-oxoPur could be also produced by a one-electron oxidation process followed by hydration of the purine radical cation thus generated, producing following oxidation mainly 8-oxodGuo due to efficient charge transfer processes (5, 6) combined with the relatively low ionization potential of guanine compared to other DNA constituents.In addition, the pioneering work of Box and coworkers (7-10) suggested the possible formation of tandem lesions, constituted of two adjacent modifications. Recent works have demonstrated that in dinucleoside monophosp...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Bergeron

Auvré

Radicella

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

123

113

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“…Finally, the interactions of an XRCC1 dimer with a LigIII␣ dimer and two molecules of Pol␤ (as well as other BER components) could give rise to two sets of active centers that could serve complementary functions in BER and SSBR. Alternatively, this complex could act at sites of clustered DNA damage, such as those generated by ionizing radiation or radiomimetic agents (48,49). Such a function could provide new testable hypotheses related to the elevated sister chromatid exchange events associated with XRCC1-deficient cells.…”

Section: Discussionmentioning

confidence: 99%

Specificity of Protein Interactions Mediated by BRCT Domains of the XRCC1 DNA Repair Protein

Beernink

Hwang

Ramirez

et al. 2005

Journal of Biological Chemistry

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Protein interactions critical to DNA repair and cell cycle control systems are often coordinated by modules that belong to a superfamily of structurally conserved BRCT domains. Because the mechanisms of BRCT interactions and their significance are not well understood, we sought to define the affinity and specificity of those BRCT modules that orchestrate base excision repair and single-strand break repair. Common to these pathways is the essential XRCC1 DNA repair protein, which interacts with at least nine other proteins and DNA. Here, we characterized the interactions of four purified BRCT domains, two from XRCC1 and their two partners from DNA ligase III␣ and poly(ADP-ribosyl) polymerase 1. A monoclonal antibody was selected that recognizes the ligase III␣ BRCT domain, but not the other BRCT domains, and was used to capture the relevant ligase III␣ BRCT complex. To examine the assembly states of isolated BRCT domains and pairwise domain complexes, we used size-exclusion chromatography coupled with on-line light scattering. This analysis indicated that isolated BRCT domains form homo-oligomers and that the BRCT complex between the C-terminal XRCC1 domain and the ligase III␣ domain is a heterotetramer with 2:2 stoichiometry. Using affinity capture and surface plasmon resonance methods, we determined that specific heteromeric interactions with high nanomolar dissociation constants occur between pairs of cognate BRCT domains. A structural model for a XRCC1⅐DNA ligase III␣ heterotetramer is proposed as a core base excision repair complex, which constitutes a scaffold for higher order complexes to which other repair proteins and DNA are brought into proximity.

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“…It has been shown that such damaged sites were difficult to be repaired with purified repair enzymes and in mammalian cells (25)(26)(27)(28)(29)(30)(31). To understand the biological significances of tandem lesions with a Tg being neighboring to an 8-oxodG, it is crucial to assess their formation and to examine the replication and repair of this type of lesions.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Thermodynamic Studies of Oligodeoxyribonucleotides Containing Tandem Lesions of Thymidine Glycol and 8-Oxo-2‘-deoxyguanosine

Wang

2006

Chem. Res. Toxicol.

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Thymidine glycol (Tg), which is also known as 5,6-dihydroxy-5,6-dihydrothymidine, and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) are two major types of DNA damage products induced by reactive oxygen species (ROS). Here we report the synthesis of oligodeoxyribonucleotides (ODNs) containing both Tg and 8-oxodG. The dual incorporation of the two single-base lesions was achieved by using a phosphoramidite building block of 8-oxodG with ultramild base protecting group and a building block of Tg whose nucleobase hydroxyl groups were protected with acetyl functionality. The availability of ODNs carrying neighboring 8-oxodG and Tg provided authentic substrates for assessing the formation and examining the replication and repair of this kind of tandem lesions. In addition, thermodynamic parameters derived from melting temperature data revealed that tandem lesions destabilized the double helix to a greater extent than either of the two single-base lesions alone. The thermodynamic results could offer a basis for understanding the repair of the tandem base lesions.

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8-OxoG retards the activity of the ligase III/XRCC1 complex during the repair of a single-strand break, when present within a clustered DNA damage site

Cited by 81 publications

References 37 publications

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Specificity of Protein Interactions Mediated by BRCT Domains of the XRCC1 DNA Repair Protein

Synthesis and Thermodynamic Studies of Oligodeoxyribonucleotides Containing Tandem Lesions of Thymidine Glycol and 8-Oxo-2‘-deoxyguanosine

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8-OxoG retards the activity of the ligase III/XRCC1 complex during the repair of a single-strand break, when present within a clustered DNA damage site

Cited by 81 publications

References 37 publications

HO • radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

HO • radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Specificity of Protein Interactions Mediated by BRCT Domains of the XRCC1 DNA Repair Protein

Synthesis and Thermodynamic Studies of Oligodeoxyribonucleotides Containing Tandem Lesions of Thymidine Glycol and 8-Oxo-2‘-deoxyguanosine

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HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases