3-Methyladenine-DNA Glycosylase (MPG Protein) Interacts with Human RAD23 Proteins

Miao, Feng; Bouziane, Mohammed; Dammann, Reinhard; Masutani, Chikahide; Hanaoka, Fumio; Pfeifer, Gerd P.; O’Connor, Timothy

doi:10.1074/jbc.m001064200

Cited by 113 publications

(74 citation statements)

References 59 publications

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“…It is possible that the abortive ⑀C⅐ANPG complex, inaccessible to BER proteins, could be processed by other DNA repair systems. For example, it has been demonstrated that the hHR23A and -B proteins, which are involved in the recognition of DNA damage in global genome-nucleotide excision repair (GG-NER) (56), interact with ANPG and elevate the rate of Hx excision (57). Therefore, the ⑀C⅐ANPG complex may direct ⑀C removal to the GG-NER pathway by recruiting the XPC⅐hHR23B complex to ⑀C via an hHR23B⅐ANPG interaction.…”

Section: Discussionmentioning

confidence: 99%

Hijacking of the Human Alkyl-N-purine-DNA Glycosylase by 3,N4-Ethenocytosine, a Lipid Peroxidation-induced DNA Adduct

Gros¹,

Maksimenko

Privezentzev³

et al. 2004

Journal of Biological Chemistry

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Lipid peroxidation generates aldehydes, which react with DNA bases, forming genotoxic exocyclic etheno(⑀)-adducts. E-bases have been implicated in vinyl chlorideinduced carcinogenesis, and increased levels of these DNA lesions formed by endogenous processes are found in human degenerative disorders. E-adducts are repaired by the base excision repair pathway. Here, we report the efficient biological hijacking of the human alkyl-N-purine-DNA glycosylase (ANPG) by 3,N 4 -ethenocytosine (⑀C) when present in DNA. Unlike the ethenopurines, ANPG does not excise, but binds to ⑀C when present in either double-stranded or single-stranded DNA. We developed a direct assay, based on the fluorescence quenching mechanism of molecular beacons, to measure a DNA glycosylase activity. Molecular beacons containing modified residues have been used to demonstrate that the ⑀C⅐ANPG interaction inhibits excision repair both in reconstituted systems and in cultured human cells. Furthermore, we show that the ⑀C⅐ANPG complex blocks primer extension by the Klenow fragment of DNA polymerase I. These results suggest that ⑀C could be more genotoxic than 1,N 6 -ethenoadenine (⑀A) residues in vivo. The proposed model of ANPG-mediated genotoxicity of ⑀C provides a new insight in the molecular basis of lipid peroxidation-induced cell death and genome instability in cancer.

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Section: Discussionmentioning

confidence: 99%

Hijacking of the Human Alkyl-N-purine-DNA Glycosylase by 3,N4-Ethenocytosine, a Lipid Peroxidation-induced DNA Adduct

Gros¹,

Maksimenko

Privezentzev³

et al. 2004

Journal of Biological Chemistry

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“…This inverted mode of DNA quality control presents the obvious advantage that the initial sensor does not need to recognize the adducts themselves and, as outlined before, actually avoids close contacts with damaged residues. The general affinity for destabilized DNA sites may facilitate other excision repair processes, as XPC has been shown to interact with 3-methyladenine DNA glycosylase [49], thymine DNA glycosylase [50] and 8-oxoguanine DNA glycosylase [6]. It is relevant to note that even a subtle 8-oxoguanine lesion perturbs the thermodynamic stability of the duplex [51].…”

Section: The Molecular Basis For Substrate Versatilitymentioning

confidence: 99%

Dynamic two-stage mechanism of versatile DNA damage recognition by xeroderma pigmentosum group C protein

Clement

Camenisch

Jia

et al. 2010

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…␤-Pol null cells were transfected with either pIRESneo or pIRESneo͞AAG, and stable populations of cells were selected with G418 (600 g͞ml). G418-resistant cultures were analyzed by Western blotting as described (20) with an AAG-specific polyclonal antibody kindly provided by Timothy R. O'Connor, City of Hope National Medical Center, Duarte, CA (25). Functional glycosylase assays were as described (26) by using a hypoxanthine containing double-stranded oligonucleotide (Trevigen, Gaithersburg, MD).…”

Section: Determination Of Mutant Frequency Atmentioning

confidence: 99%

Mutations associated with base excision repair deficiency and methylation-induced genotoxic stress

Sobol

Watson

Nakamura

et al. 2002

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

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The long-term effect of exposure to DNA alkylating agents is entwined with the cell's genetic capacity for DNA repair and appropriate DNA damage responses. A unique combination of environmental exposure and deficiency in these responses can lead to genomic instability; this ''gene-environment interaction'' paradigm is a theme for research on chronic disease etiology. In the present study, we used mouse embryonic fibroblasts with a gene deletion in the base excision repair (BER) enzymes DNA ␤-polymerase (␤-pol) and alkyladenine DNA glycosylase (AAG), along with exposure to methyl methanesulfonate (MMS) to study mutagenesis as a function of a particular gene-environment interaction. The ␤-pol null cells, defective in BER, exhibit a modest increase in spontaneous mutagenesis compared with wild-type cells. MMS exposure increases mutant frequency in ␤-pol null cells, but not in isogenic wild-type cells; UV light exposure or N-methyl-N -nitro-N-nitrosoguanidine exposure increases mutant frequency similarly in both cell lines. The MMS-induced increase in mutant frequency in ␤-pol null cells appears to be caused by DNA lesions that are AAG substrates, because overexpression of AAG in ␤-pol null cells eliminates the effect. In contrast, ␤-pol͞AAG double null cells are slightly more mutable than the ␤-pol null cells after MMS exposure. These results illustrate that BER plays a role in protecting mouse embryonic fibroblast cells against methylation-induced mutations and characterize the effect of a particular combination of BER gene defect and environmental exposure. B ase excision repair (BER) (1) is considered the predominant DNA repair system in mammalian cells for eliminating small DNA lesions generated either exogenously or endogenously at DNA bases (1-3). Such DNA damage can be caused by exposure to environmental agents or by normal cellular metabolic processes that produce reactive oxygen species, alkylating molecules, and other reactive metabolites capable of modifying DNA. The first two steps of the mammalian BER pathway are removal of a damaged base residue by a DNA glycosylase and subsequent action of apurinic͞apyrimidinic (AP) endonuclease. The product of these reactions is single-nucleotide gapped DNA with 5Ј deoxyribosephosphate (dRP) and 3Ј OH at the margins of the gap. A DNA ␤-polymerase (␤-pol)-mediated DNA synthesis step fills the single-nucleotide gap (4-6), and the 5Ј dRP group is removed by the dRP lyase activity of ␤-pol (7-11). DNA ligase I or III conducts the final, nick-sealing step in the pathway. Many laboratories have presented evidence in support of the roles of the enzymes noted here in single-nucleotide BER, mediated either by crude cell extracts or purified enzymes (3, 4, 12-16). Another important feature of single-nucleotide BER is that some of the enzymes in the pathway can interact with each other, forming a series of ''subassemblies'' that may pass along the substrates and products like a baton in a relay (for review, see ref. 17).It is well known that ␤-pol null mouse cells are hypersen...

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3-Methyladenine-DNA Glycosylase (MPG Protein) Interacts with Human RAD23 Proteins

Cited by 113 publications

References 59 publications

Hijacking of the Human Alkyl-N-purine-DNA Glycosylase by 3,N4-Ethenocytosine, a Lipid Peroxidation-induced DNA Adduct

Hijacking of the Human Alkyl-N-purine-DNA Glycosylase by 3,N4-Ethenocytosine, a Lipid Peroxidation-induced DNA Adduct

Dynamic two-stage mechanism of versatile DNA damage recognition by xeroderma pigmentosum group C protein

Mutations associated with base excision repair deficiency and methylation-induced genotoxic stress

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