Immunofluorescent localization of the murine 8-oxoguanine DNA glycosylase (mOGG1) in cells growing under normal and nutrient deprivation conditions

Conlon, Kimberly A.; Zharkov, Dmitry O.; Berríos, Miguel

doi:10.1016/j.dnarep.2003.08.002

Cited by 24 publications

(20 citation statements)

References 52 publications

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“…Consistent with previous reports, untreated cells have an endogenous background level of 8-oxoG (Fig. 5D) (28,30,49). The levels of 8-oxoG were similar to untreated cells when cells were incubated with the PARP inhibitor ABT-888.…”

Section: Parp-1 Interacts With Ogg1 In Vitro and In Vivo-supporting

confidence: 91%

Poly(ADP-ribose) Polymerase 1 (PARP-1) Binds to 8-Oxoguanine-DNA Glycosylase (OGG1)

Hooten

Kompaniez

Barnes

et al. 2011

Journal of Biological Chemistry

106

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Background: Oxidative stress-induced DNA damage is repaired by proteins in the base excision pathway. Results: We identified a novel interaction between two DNA repair proteins, OGG1 and PARP-1. Conclusion: OGG1-PARP-1 binding has both a functional and biological consequence. Significance: These results provide insight into the factors that regulate DNA repair under normal and oxidative stress conditions.

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Section: Parp-1 Interacts With Ogg1 In Vitro and In Vivo-supporting

confidence: 91%

Poly(ADP-ribose) Polymerase 1 (PARP-1) Binds to 8-Oxoguanine-DNA Glycosylase (OGG1)

Hooten

Kompaniez

Barnes

et al. 2011

Journal of Biological Chemistry

106

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“…The subcellular distribution of a number of DNA damage signaling and repair proteins changes in response to DNA damage (32)(33)(34)(35)(36). Results in this study have demonstrated a specific DNA damage-induced cytoplasmic to nuclear transport of two proteins involved in the catalysis of HR-mediated DNA repair, Rad51 and Rad51C.…”

Section: Discussionmentioning

confidence: 67%

“…Numerous studies show the presence of significant amounts of cytoplasmic Rad51 in normal cycling cells (23)(24)(25)(26)(27)(28)(29)(30)(31), suggesting that the level of nuclear Rad51 is controlled by regulated changes in its subcellular distribution. In fact, exposure of cells to DNA-damaging agents has been shown to elicit movement of numerous DNA damage signaling proteins, cell cycle checkpoint effectors, and DNAprocessing enzymes among various cellular compartments (32), including the cytoplasmic to nuclear transport of proteins involved in DNA base excision repair (33,34) and DNA mismatch repair (35,36). Although localized nuclear responses to DNA damage by many DSB signaling and repair proteins, including ATM, Chk2, the Mre11-Rad50-Nbs1 complex, MDC1, 53BP1, and Rad51, have been well documented (26,(37)(38)(39)(40)(41)(42)(43), the possible contribution of a cytoplasmic to nuclear transport of DSB repair proteins to this response has not been fully considered.…”

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confidence: 99%

Cellular Redistribution of Rad51 in Response to DNA Damage

Gildemeister

Sage

Knight

2009

Journal of Biological Chemistry

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Exposure of cells to DNA-damaging agents results in a rapid increase in the formation of subnuclear complexes containing Rad51. To date, it has not been determined to what extent DNA damage-induced cytoplasmic to nuclear transport of Rad51 may contribute to this process. We have analyzed subcellular fractions of HeLa and HCT116 cells and found a significant increase in nuclear Rad51 levels following exposure to a modest dose of ionizing radiation (2 grays). We also observed a DNA damageinduced increase in nuclear Rad51 in the Brca2-defective cell line Capan-1. To address a possible Brca2-independent mechanism for Rad51 nuclear transport, we analyzed subcellular fractions for two other Rad51-interacting proteins, Rad51C and Xrcc3. Rad51C has a functional nuclear localization signal, and although we found that the subcellular distribution of Xrcc3 was not significantly affected by DNA damage, there was a damageinduced increase in nuclear Rad51C. Furthermore, RNA interference-mediated depletion of Rad51C in HeLa and Capan-1 cells resulted in lower steady-state levels of nuclear Rad51 as well as a diminished DNA damage-induced increase. Our results provide important insight into the cellular regulation of Rad51 nuclear entry and a role for Rad51C in this process.Cellular surveillance of genome integrity and repair of DNA damage are essential processes that ensure proper development and survival of all organisms. DNA double-strand breaks (DSBs) 2 are a particularly deleterious form of genome damage and occur following exposure of cells to exogenous mutagens as well as during normal metabolic processes, e.g. antigen receptor gene rearrangement, restart of stalled replication forks, formation of meiotic DNA crossovers, etc. (1, 2). Mammalian cells use two distinct mechanisms for repair of DSBs, non-homologous end joining and homologous recombination (HR). Processes requiring imprecise DNA repair, such as the creation of antibody diversity, exploit the error-prone non-homologous end joining mechanism. In contrast, HR is an error-free DNA repair pathway and is critical for avoidance of unwanted genetic changes during the meiotic exchange of information between paternal and maternal alleles and for error-free repair of broken chromosomes (3). Rad51 is the central enzymatic component of HR. Upon its regulated recruitment to sites of DNA breaks, Rad51 forms a nucleoprotein filament by polymerizing onto single-stranded DNA at the processed break. This filament catalyzes DNA strand exchange with an undamaged sister chromatid or homologous chromosome, which serves as a template for the restoration of missing genetic information (3, 4).Visible nuclear Rad51 clusters, or foci, form during S-phase and appear to localize to sites of replicating DNA (5-7). A dramatic increase in the number and size of nuclear Rad51 foci is a hallmark of the early cellular response to genomic insult (7-10). The appearance of DNA damage-induced nuclear Rad51 foci is blocked in cells with deficiencies in several HR-related proteins, including Brca2 ...

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“…For comparison, the fluorescence of scr-siRNA cells exposed to 500 M H 2 O 2 for 30 min, a situation that induces high levels of 8-oxoG, is presented. Other laboratories using the same methodology have also demonstrated a punctuate pattern, with the signal more intense on the periphery of the nucleus, probably at heterochromatic DNA (7,32,40; see also the Trevigen web site). For the control, the results for the DAPI signal and the secondary antibody-only control are also presented.…”

mentioning

confidence: 85%

The Recombination Protein RAD52 Cooperates with the Excision Repair Protein OGG1 for the Repair of Oxidative Lesions in Mammalian Cells

Souza-Pinto

Maynard

Hashiguchi

et al. 2009

Molecular and Cellular Biology

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Oxidized bases are common types of DNA modifications. Their accumulation in the genome is linked to aging and degenerative diseases. These modifications are commonly repaired by the base excision repair (BER) pathway. Oxoguanine DNA glycosylase (OGG1) initiates BER of oxidized purine bases. A small number of protein interactions have been identified for OGG1, while very few appear to have functional consequences. We report here that OGG1 interacts with the recombination protein RAD52 in vitro and in vivo. This interaction has reciprocal functional consequences as OGG1 inhibits RAD52 catalytic activities and RAD52 stimulates OGG1 incision activity, likely increasing its turnover rate. RAD52 colocalizes with OGG1 after oxidative stress to cultured cells, but not after the direct induction of double-strand breaks by ionizing radiation. Human cells depleted of RAD52 via small interfering RNA knockdown, and mouse cells lacking the protein via gene knockout showed increased sensitivity to oxidative stress. Moreover, cells depleted of RAD52 show higher accumulation of oxidized bases in their genome than cells with normal levels of RAD52. Our results indicate that RAD52 cooperates with OGG1 to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. Our observations suggest a coordinated action between these proteins that may be relevant when oxidative lesions positioned close to strand breaks impose a hindrance to RAD52 catalytic activities.Oxidative DNA damage is generated at high levels in mammalian cells, even in cells not exposed to exogenous sources of reactive oxygen species. Several kinds of DNA modifications are formed upon oxidative stress (8). The most prevalent modifications, quantitatively, are single-strand breaks and oxidized bases. Clustered DNA damage, when two or more modifications are closely positioned in opposite strands, is detectable after gamma irradiation and has recently been shown to be generated by normal oxidative metabolism (3,35). One unique aspect of such clustered lesions is that they can be converted into double-strand breaks (DSB) if a DNA glycosylase removes the two opposite bases and an apurinic/apyrimidinic (AP)-endonuclease cleaves the resulting abasic sites. Thus, although quantitatively minor, DSB are possible outcomes of oxidative DNA damage.

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Immunofluorescent localization of the murine 8-oxoguanine DNA glycosylase (mOGG1) in cells growing under normal and nutrient deprivation conditions

Cited by 24 publications

References 52 publications

Poly(ADP-ribose) Polymerase 1 (PARP-1) Binds to 8-Oxoguanine-DNA Glycosylase (OGG1)

Poly(ADP-ribose) Polymerase 1 (PARP-1) Binds to 8-Oxoguanine-DNA Glycosylase (OGG1)

Cellular Redistribution of Rad51 in Response to DNA Damage

The Recombination Protein RAD52 Cooperates with the Excision Repair Protein OGG1 for the Repair of Oxidative Lesions in Mammalian Cells

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