DNA?protein crosslinks: their induction, repair, and biological consequences

Barker, Sharon; Weinfeld, Michael; Murray, David

doi:10.1016/j.mrrev.2004.11.003

Cited by 277 publications

(327 citation statements)

References 143 publications

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“…Proteins can become cross-linked to DNA directly through oxidative free radical mechanisms. 45 DPCs can be formed by topoisomerase inhibitors; yet, previous studies have shown that DPCs induced by AF are unrelated to topoisomerase cleavage complexes. 8 Previous studies have characterized and identified covalent drug adducts which indicates that AF metabolite(s) alkylate DNA.…”

Section: Discussionmentioning

confidence: 94%

Aminoflavone induces oxidative DNA damage and reactive oxidative species‐mediated apoptosis in breast cancer cells

McLean

Soto

Agama

et al. 2008

Intl Journal of Cancer

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686288), a novel anticancer candidate agent, is undergoing clinical evaluation. AF induces DNA-protein cross-links (DPCs), c-H2AX phosphorylation, aryl hydrocarbon receptor (AhR) signaling, apoptosis and its own metabolism via cytochrome P4501A1 and 1A2 (CYP1A1/1A2) activation in sensitive estrogen receptor positive (ER1) MCF7 breast cancer cells. Estrogen receptor negative (ER2) breast cancer is typically more aggressive with a poorer prognosis. In this investigation, we evaluated the ability of AF to induce reactive oxygen species (ROS) formation, oxidative DNA damage and apoptosis in ER2 MDA-MB-468 breast cancer cells. The antioxidant, N-acetyl-L-cysteine (NAC), attenuated the cytotoxic effects of AF in MDA-MB-468 cells; an effect is also observed in ER1 T47D breast cancer cells. Nonmalignant MCF10A breast epithelial cells were resistant to the cytotoxic effects of AF. AF increased intracellular ROS, an effect blocked by NAC and the CYP1A1/1A2 inhibitor, a-Naphthoflavone (a-NF). AF induced oxidative DNA damage as evidenced by increased 8-oxo-7,8-dihydroguanine (8-oxodG) levels and DPC formation in these cells. AF caused S-phase arrest corresponding to an increase in p21 (waf1/cip1) protein expression. AF induced caspase 3, 8 and 9 activation, caspase-dependent apoptotic body formation and poly [ADP-ribose] polymerase (PARP) cleavage. Pretreatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp(OMe)-fluoromethylketone inhibited apoptosis and partially inhibited ROS formation and oxidative DNA damage. Pretreatment with NAC attenuated AF-induced apoptotic body formation and caspase 3 activation. These studies suggest AF inhibits the growth of breast cancer cells in part, by inducing ROS production, oxidative DNA damage and apoptosis and has the potential to treat hormone-independent breast cancer. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 94%

Aminoflavone induces oxidative DNA damage and reactive oxidative species‐mediated apoptosis in breast cancer cells

McLean

Soto

Agama

et al. 2008

Intl Journal of Cancer

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“…Covalent entrapment of cellular proteins on genomic DNA is a common process that occurs upon exposure to a variety of endogenous and exogenous bis-electrophiles, heavy metals, and free radicals (1)(2)(3)(4)(5)(6)(7). 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).…”

mentioning

confidence: 99%

“…Because of their enormous size as compared with other nucleobase lesions and their ability to disrupt DNA duplex structure and DNA-protein interactions, DPCs are hypothesized to interfere with DNA replication and transcription (1,2). We reported previously that protein monoepoxide reagents that selectively induce DPC lesions cause toxicity and mutations in human cells (18).…”

mentioning

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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“…Although the reason for this is unclear, it may have been caused by differences in the type of enhanced DNA repair in the cells that developed resistance to both radiation types versus the cells specifically that became resistant to carbon ions only. For example, complex DNA damage may contain a crosslink product such as DNAprotein crosslink (DPC) (18,19). If such a product is yielded by repeated exposure to high-dose X rays and the removal capacity of DPC, which is associated with nucleotide excision repair and homologous recombination repair (20), is selectively enhanced in X60-D4, X60-A9 and X60-4 cells, these cells might develop resistance only to Cion radiation.…”

Section: Features Of X-ray and Carbon-ion Resistant Cancer Cellsmentioning

confidence: 99%

High-LET Irradiation of a DNA-Binding Protein: Protein-Protein and DNA-Protein Crosslinks

Culard¹,

Bouffard²,

Charlier³

2005

Radiation Research

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DNA?protein crosslinks: their induction, repair, and biological consequences

Cited by 277 publications

References 143 publications

Aminoflavone induces oxidative DNA damage and reactive oxidative species‐mediated apoptosis in breast cancer cells

Aminoflavone induces oxidative DNA damage and reactive oxidative species‐mediated apoptosis in breast cancer cells

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

High-LET Irradiation of a DNA-Binding Protein: Protein-Protein and DNA-Protein Crosslinks

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