Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin

Donahue, Brian A.; Augot, Marianne; Bellon, Steven F.; Treiber, Daniel K.; Toney, Jeffrey H.; Lippard, Stephen J.; Essigmann, John M.

doi:10.1021/bi00476a032

Cited by 141 publications

(138 citation statements)

References 35 publications

(50 reference statements)

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“…The digested 123-base pair fragment containing 4-bp 5Ј-overhangs was purified on a 10% native polyacrylamide gel, ethanol-precipitated, and quantitated by UV-vis spectroscopy (Hewlett Packard 8453). The purified probe was modified with cisplatin or trans-DDP at various platinum:nucleotide ratios (r f , added platinum:nucleotide ratio) following published procedures (26). The extent of platination (r b , bound platinum:nucleotide ratio) was determined by flameless atomic absorption spectroscopy (PerkinElmer Life Sciences HGA-800 AAnalyst 300) and UV-vis spectroscopy.…”

Section: Methodsmentioning

confidence: 99%

Interaction of FACT, SSRP1, and the High Mobility Group (HMG) Domain of SSRP1 with DNA Damaged by the Anticancer Drug Cisplatin

Yarnell¹,

Oh²,

Reinberg³

et al. 2001

Journal of Biological Chemistry

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The structure-specific recognition protein SSRP1, initially isolated from expression screening of a human B-cell cDNA library for proteins that bind to cisplatin (cis-diamminedichloroplatinum(II))-modified DNA, contains a single DNA-binding high mobility group (HMG) domain. Human SSRP1 purifies as a heterodimer of SSRP1 and Spt16 (FACT) that alleviates the nucleosomal block to transcription elongation by RNAPII in vitro. The affinity and specificity of FACT, SSRP1, and the isolated HMG domain of SSRP1 for cisplatin-damaged DNA were investigated by gel mobility shift assays. FACT exhibits both affinity and specificity for DNA damaged globally with cisplatin compared with unmodified DNA or DNA damaged globally with the clinically ineffective trans-DDP isomer. FACT binds the major 1,2-d(GpG) intrastrand cisplatin adduct, but its isolated SSRP1 subunit fails to form discrete, high affinity complexes with cisplatin-modified DNA under similar conditions. These results suggest that Spt16 primes SSRP1 for cisplatin-damaged DNA recognition by unveiling its HMG domain. As expected, the isolated HMG domain of SSRP1 is sufficient for specific binding to cisplatin-damaged DNA and binds the major cisplatin 1,2-d(GpG) intrastrand cross-link. The affinity and specificity of FACT for cisplatin-modified DNA, as well as its importance for transcription of chromatin, suggests that the interaction of FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin.

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Section: Methodsmentioning

confidence: 99%

Interaction of FACT, SSRP1, and the High Mobility Group (HMG) Domain of SSRP1 with DNA Damaged by the Anticancer Drug Cisplatin

Yarnell¹,

Oh²,

Reinberg³

et al. 2001

Journal of Biological Chemistry

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“…This sequence is likely initiated or facilitated following the recognition of DNA damage by over 20 individual candidate proteins, which bind to physical distortions in the DNA that are induced by the intrastrand platinum adducts (Bellon et al, 1991). These damage recognition proteins include the hMSH2 or hMutSa component of the mismatch repair (MMR) complex, the nonhistone chromosomal high-mobility group 1 and 2 (HMG1 and HMG2) proteins, the human RNA polymerase I transcription 'upstream binding factor' (hUBF), and the transcriptional factor 'TATA binding protein' (TBP) (Donahue et al, 1990;Fink et al, 1998;Chaney and Vaisman, 1999). Whether a single protein or combinations of these are involved in sensing the damage is not clear.…”

Section: Dna Adducts and Damage Recognitionmentioning

confidence: 99%

Cisplatin: mode of cytotoxic action and molecular basis of resistance

2003

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Cisplatin is one of the most potent antitumor agents known, displaying clinical activity against a wide variety of solid tumors. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of cisplatinbased chemotherapy. The mechanisms responsible for cisplatin resistance are several, and contribute to the multifactorial nature of the problem. Resistance mechanisms that limit the extent of DNA damage include reduced drug uptake, increased drug inactivation, and increased DNA adduct repair. Origins of these pharmacologicbased mechanisms, however, are at the molecular level. Mechanisms that inhibit propagation of the DNA damage signal to the apoptotic machinery include loss of damage recognition, overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3-K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and interference in caspase activation. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance.

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“…In contrast, DNA adducts of photoactivated 1 (presumably similar to those formed by conventional transplatin, i.e. mainly 1,3- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 intrastrand CLs, monofunctional adducts and to a much lesser extent interstrand CLs, Table 1) rather produce in DNA flexible and relatively small nondirectional bends so that these adducts are not recognized by HMG-domain proteins (60)(61)(62). Hence, DNA adducts of photoactivated 1 may lack, in contrast to DNA adducts of cisplatin, a high-affinity structural motif which would attract transcription factors.…”

Section: Adducts Such As Trans-[pt(py)mentioning

confidence: 99%

Interactions of DNA with a New Platinum(IV) Azide Dipyridine Complex Activated by UVA and Visible Light: Relationship to Toxicity in Tumor Cells

Prachařová

Zerzánková

Štěpánková

et al. 2012

Chem. Res. Toxicol.

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The Pt IV diazido complex trans,trans,trans-[Pt-(N 3 ) 2 (OH) 2 (pyridine) 2 ] (1) is unreactive in the dark but is cytotoxic when photoactivated by UVA and visible light. We have shown that 1 when photoactivated accumulates in tumor cells and binds strongly to nuclear DNA under conditions in which it is toxic to tumor cells. The nature of the DNA adducts, including conformational alterations, induced by photoactivated 1 are distinctly different from those produced in DNA by conventional cisplatin or transplatin. In addition, the observation that major DNA adducts of photoactivated 1 are able to efficiently stall RNA polymerase II more efficiently than cisplatin suggests that transcription inhibition may contribute to the cytotoxicity levels observed for photoactivated 1. Hence, DNA adducts of 1 could trigger a number of downstream cellular effects different from those triggered in cancer cells by DNA adducts of cisplatin. This might lead to the therapeutic effects that could radically improve chemotherapy by platinum complexes. The findings of the present work help to explain the different cytotoxic effects of photoactivated 1 and conventional cisplatin and thereby provide new insights into mechanisms associated with the antitumor effects of platinum complexes photoactivated by UVA and visible light.

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Characterization of a DNA damage-recognition protein from mammalian cells that binds specifically to intrastrand d(GpG) and d(ApG) DNA adducts of the anticancer drug cisplatin

Cited by 141 publications

References 35 publications

Interaction of FACT, SSRP1, and the High Mobility Group (HMG) Domain of SSRP1 with DNA Damaged by the Anticancer Drug Cisplatin

Interaction of FACT, SSRP1, and the High Mobility Group (HMG) Domain of SSRP1 with DNA Damaged by the Anticancer Drug Cisplatin

Cisplatin: mode of cytotoxic action and molecular basis of resistance

Interactions of DNA with a New Platinum(IV) Azide Dipyridine Complex Activated by UVA and Visible Light: Relationship to Toxicity in Tumor Cells

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