Structure of a hydroxyl radical-induced DNA-protein crosslink involving thymine and tyrosine in nucleohistone

Dizdaroğlu, Miral; Gajewski, Ewa; Reddy, P.G.; Margolis, Sam A.

doi:10.1021/bi00434a071

Cited by 126 publications

(91 citation statements)

References 16 publications

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“…First, the protein may be linked to the phosphodiester backbone at a nick (topo I and Pol ␤) or a double-strand break (topo II and Spo11) (1)(2)(3)(4)10). Second, the protein may be crosslinked to an oxidized base as in the case of T4-pdg, and presumably the crosslinks that are formed by ionizing radiation and oxidative stress (5,6,12,13). Third, the protein may be crosslinked to the base, as occurs with the nitrosative deamination product of guanine, oxanine, which reacts with amino groups of DNA-binding proteins (11).…”

Section: Discussionmentioning

confidence: 99%

“…Two potentially abundant lesions in eukaryotic cells are the amide link between Pol ␤ and 2-deoxy-ribonolactone that is generated after cleavage of an oxidized AP site by Ape1 (10) and the nitric oxide-induced deamination of guanine to yield oxanine, which reacts with the amine groups of any DNA-binding protein to form an amide bond (11). The natures of many drug-induced crosslinks can be inferred, although there are only a limited number of studies on the structures of these lesions (12,13). Similarly, there are only a few studies on the repair of these pathological DNA-protein crosslinks, and these studies have not provided a unified model.…”

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confidence: 99%

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Repair of DNA–polypeptide crosslinks by human excision nuclease

Reardon

Sancar

2006

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

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DNA-protein crosslinks are relatively common DNA lesions that form during the physiological processing of DNA by replication and recombination proteins, by side reactions of base excision repair enzymes, and by cellular exposure to bifunctional DNA-damaging agents such as platinum compounds. The mechanism by which pathological DNA-protein crosslinks are repaired in humans is not known. In this study, we investigated the mechanism of recognition and repair of protein-DNA and oligopeptide-DNA crosslinks by the human excision nuclease. Under our assay conditions, the human nucleotide excision repair system did not remove a 16-kDa protein crosslinked to DNA at a detectable level. However, 4-and 12-aa-long oligopeptides crosslinked to the DNA backbone were recognized by some of the damage recognition factors of the human excision nuclease with moderate selectivity and were excised from DNA at relatively efficient rates. Our data suggest that, if coupled with proteolytic degradation of the crosslinked protein, the human excision nuclease may be the major enzyme system for eliminating protein-DNA crosslinks from the genome.damage recognition ͉ nucleotide excision repair D NA-protein crosslinks are intermediates in the reaction pathways of certain enzymes such as integrases, topoisomerases, and meiotic recombinases (1-4). In addition, crosslinks are induced by DNA-damaging agents including ionizing radiation, UV light, metals such as chromium and arsenic (5, 6), and bifunctional chemotherapeutic drugs such as platinum compounds and nitrogen mustards (7-9). Finally, crosslinks may form when repair enzymes attempt to process aldehyde groups either in the DNA backbone in the form of apurinic͞ apyrimidinic (AP) sites or on oxidized nucleobase residues (10).The repair of some of these DNA-protein crosslinks is well understood: the topoisomerase I-DNA 3Ј tyrosyl-phosphodiester is commonly cleaved in the normal course of the topoisomerase (topo) reaction. However, when topo cleaves DNA near lesions such as pyrimidine dimers or nicks, the enzyme-DNA crosslink is frozen in transit, giving rise to a stable crosslink at a single-stranded nick site. This lesion is repaired by a remarkable enzyme called tyrosyl-DNA phosphodiesterase, Tdp1 (1). Tdp1 cleaves the 3Ј tyrosyl-phosphodiester bond and converts it to a 3Ј phosphate terminus, which is then processed to a 3Ј OH that can be ligated. Tdp1 has also been implicated in the removal of other 3Ј adducts (2). The enzyme has been found in all eukaryotes tested in which a topo I-3Ј tyrosylphosphodiester bond forms in the course of the reaction but not in prokaryotes in which the reaction intermediate is a topo I-DNA 5Ј tyrosyl-phosphodiester (3).DNA-protein crosslinks can also form during meiosis. Spo11 in yeast (SPO11 in mammals) makes a staggered double-strand break to initiate meiotic recombination; each subunit of the dimeric protein is linked to the resulting 5Ј ends through a 5Ј tyrosyl-phosphodiester linkage. In contrast to the topo I-3Ј tyrosyl-phosphodiester complex, the Spo11-...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Repair of DNA–polypeptide crosslinks by human excision nuclease

Reardon

Sancar

2006

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

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“…Gamma radiation damages DNA indirectly through the production of free radicals (23), and the conformation of DNA and DNA-protein interactions could affect the damage created by free radicals (24).…”

Section: Comparison Between Neutron and Gamma Radiation In Ras Mutatimentioning

confidence: 99%

ras activation in human tumors and in animal model systems.

Corominas

Sloan

León

et al. 1991

Environ Health Perspect

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Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. We have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbezanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. We found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel Kras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation.

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“…Specifically, common chemotherapeutics such as nitrogen mustards, platinum compounds, and alkylnitrosoureas (3,4,8); environmental carcinogens such as formaldehyde and 1,3-butadiene (5, 9, 10); toxic metals (11)(12)(13); nitric oxide (14); free radicals (15,16); UV light (17); and ionizing radiation (6) mediate the formation of covalent DNAprotein cross-links (DPCs). 3 Mass spectrometry-based proteomic studies have identified a large number of cellular proteins that participate in DPC formation in cells treated with cross-linking agents, including DNA repair proteins, DNA polymerases, transcription factors, and structural proteins such as histones, heat shock proteins, and tubulins (3-6, 8, 10).…”

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confidence: 99%

Bypass of DNA-Protein Cross-links Conjugated to the 7-Deazaguanine Position of DNA by Translesion Synthesis Polymerases

Wickramaratne

Mukherjee

et al. 2016

Journal of Biological Chemistry

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DNA-protein cross-links (DPCs) are bulky DNA lesions that form both endogenously and following exposure to bis-electrophiles such as common antitumor agents. The structural and biological consequences of DPCs have not been fully elucidated due to the complexity of these adducts. The most common site of DPC formation in DNA following treatment with bis-electrophiles such as nitrogen mustards and cisplatin is the N7 position of guanine, but the resulting conjugates are hydrolytically labile and thus are not suitable for structural and biological studies. In this report, hydrolytically stable structural mimics of N7-guanine-conjugated DPCs were generated by reductive amination reactions between the Lys and Arg side chains of proteins/peptides and aldehyde groups linked to 7-deazaguanine residues in DNA. These model DPCs were subjected to in vitro replication in the presence of human translesion synthesis DNA polymerases. DPCs containing full-length proteins (11-28 kDa) or a 23-mer peptide blocked human polymerases and . DPC conjugates to a 10-mer peptide were bypassed with nucleotide insertion efficiency 50 -100-fold lower than for native G. Both human polymerase (hPol) and hPol inserted the correct base (C) opposite the 10-mer peptide cross-link, although small amounts of T were added by hPol . Molecular dynamics simulation of an hPol ternary complex containing a template-primer DNA with dCTP opposite the 10-mer peptide DPC revealed that this bulky lesion can be accommodated in the polymerase active site by aligning with the major groove of the adducted DNA within the ternary complex of polymerase and dCTP.

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Structure of a hydroxyl radical-induced DNA-protein crosslink involving thymine and tyrosine in nucleohistone

Cited by 126 publications

References 16 publications

Repair of DNA–polypeptide crosslinks by human excision nuclease

Repair of DNA–polypeptide crosslinks by human excision nuclease

ras activation in human tumors and in animal model systems.

Bypass of DNA-Protein Cross-links Conjugated to the 7-Deazaguanine Position of DNA by Translesion Synthesis Polymerases

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