A d(GpG)‐platinated decanucleotide duplex is kinked

Herman, Frédéric; Kozelka, Jiřarí; Stoven, Véronique; Guittet, Éric; Girault, Jean‐Pierre; Huynh‐Dinh, Tam; Igolen, J.; Lallemand, Jean‐Yves; Chottard, Jean‐Claude

doi:10.1111/j.1432-1033.1990.tb19435.x

Cited by 108 publications

(109 citation statements)

References 47 publications

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“…The CP-GG and OX-GG adducts that we have studied (17, 18) (manuscript in preparation) are similar to all other Pt-GG structures reported to date in that they display an increase in roll at the G6-G7 base-pair step, G6-G7 dihedral angle and overall bend angle compared to undamaged DNA (19)(20)(21)(22)(23). We hypothesize that these common conformational features of Pt-GG adducts, which are centered around the G6-G7 base-pair step, are important for recognition of both CP-and OX-GG adducts by DNA-binding proteins.…”

Section: Dna Helical Parameters Common To All Pt-gg Adductssupporting

confidence: 50%

Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts

Chaney

Ramachandran

Sharma

et al. 2009

Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy

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Some DNA damage-recognition proteins, transcription factors, mismatch repair proteins and DNA polymerases discriminate between cisplatin (CP)-and oxaliplatin (OX)-GG DNA adducts, and this is thought to help explain differences in efficacy, toxicity and mutagenicity of CP and OX. In addition, differential recognition of CP-and OX-GG adducts by some proteins has been shown to be highly dependent on the sequence context of the Pt-GG adduct. We have postulated that CP-and OX-GG adducts cause differences in the conformation and/or conformational dynamics of the DNA that provide the basis for differential protein recognition of the adducts. We have determined the NMR solution structure of CP-GG adducts, OX-GG adducts and undamaged DNA in the AGGC sequence context, and of OX-GG adducts and undamaged DNA in the TGGT sequence context. We have also employed molecular dynamics (MD) simulations to investigate the conformational dynamics of CP-GG adducts, OX-GG adducts and undamaged DNA in the AGGC and TGGA sequence contexts. These studies showed clear differences in the conformation dynamics between CP-and OX-GG adducts which correlated with the average conformational differences observed in the NMR solution structures and with conformations previously reported for the CP-GG DNA·HMG1a complex. When the conformational dynamics in both sequence contexts were compared it became evident that: (a) the patterns of hydrogen bond formation between Pt-amine-hydrogens and surrounding bases of the DNA were different for CP-and OX-GG adducts; (b) patterns of hydrogen bond formation were also influenced by the DNA sequence context of the Pt-GG adducts, and (c) differences in patterns of hydrogen bond formation were highly correlated with differences in the conformational dynamics of the adduct. Thus, we postulate that patterns of hydrogen bond formation between Pt-amine hydrogens and surrounding DNA bases are different for CP-and OX-GG adducts, and that those differences in hydrogen bond patterns result in DNA conformational differences that allow selective recognition of CP-and

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Section: Dna Helical Parameters Common To All Pt-gg Adductssupporting

confidence: 50%

Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts

Chaney

Ramachandran

Sharma

et al. 2009

Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy

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“…Herman et al [28] have reported that in the C~S-[P~(NH,),]~+ chelate of the decanucleotide duplex d(GCCPt7GPt7GATCGC) . d(CGGCCTAGCG), the C residue complementary to the 5'G is mobile and can stack on either branch of the kinked complementary strand.…”

Section: Discussionmentioning

confidence: 99%

“…The conformational changes involved in the formation of platinated GG chelates have been elucidated recently in solution and in the crystalline state. In the X-ray structure [26] [28].…”

Section: Discussionmentioning

confidence: 99%

Structural Transitions of a GG‐Platinated DNA Duplex Induced by pH, Temperature and Box A of High‐Mobility‐Group Protein 1

Berners‐Price¹,

Corazza²,

Guo³

et al. 1997

European Journal of Biochemistry

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[1H,15N] and 1H NMR, and CD spectroscopy are used to show that the duplex d(A‐T‐A‐C‐A‐T‐Pt7G‐Pt7G‐T‐A‐C‐A‐T‐A) ˙ d(T‐A‐T‐G‐T‐A‐C‐C‐A‐T‐G‐T‐A‐T), where Pt7G is platinated guanine, containing the cis‐[Pt(NH3)2]2+ adduct undergoes reversible temperature‐induced (T0.5 310 K) and pH‐induced (pKa≈ 4.8) transitions between kinked‐duplex and distorted forms, with the latter forms predominating at high temperature and low pH. A related pH‐induced structural change was observed for the unplatinated duplex (pKa 4.69, Hill coefficient n= 1.4) but was less cooperative than for the platinated duplex (n= 2). The pH‐induced transition is attributed to protonation of cytosine residues and has wider implications, since many reported NMR studies of DNA are carried out near pH 5 to minimize NH‐exchange rates. The [Pt(en)]2+ (where en is 1,2‐ethanediamine) GG chelate of the same duplex is shown to exist in kinked and distorted forms, and the [1H,15N]‐NMR shifts for the kinked form are indicative of the presence of highly stereospecific interactions with the Pt‐NH protons. On binding of the duplex platinated with [Pt(NH3)2]2+ to high‐mobility‐group protein 1 (HMG1) box A, similar changes in shifts of the Pt‐NH3 resonances to those induced by raising the temperature or lowering the pH were observed. The specific changes in 1H‐NMR chemical shifts of HMG1 box A are consistent with binding of the platinated duplex (intermediate exchange rate on the 1H‐NMR time‐scale) to the concave face of the protein via helices I and II and the intervening loop.

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“…Previous crystallographic, NMR, and gel electrophoretic investigations have evaluated the impact of this crosslink on the structure and conformation of the host duplex (1)(2)(3)(4)(5)(6)(7)(8)(9). These studies indicate that formation of the cis-Pt-GG crosslink unwinds DNA by 130 and bends it by 34-55°in the direction of the major groove.…”

Section: N7(1) -N7(2)}] (Cis-pt-gg)mentioning

confidence: 99%

Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex.

Poklar

Pilch

Lippard

et al. 1996

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

186

142

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ABSTRACTcis-Diamminedichloroplatinum(II) (cisplatin) is a widely used anticancer drug that binds to and crosslinks DNA. The major DNA adduct of the drug results from coordination of two adjacent guanine bases to platinum to form the intrastrand crosslink cis-[Pt(NH3)2{d(GpG)-N7(1), -N7(2)}] (cis-Pt-GG). In the present study, spectroscopic and calorimetric techniques were employed to characterize the influence of this crosslink on the conformation, thermal stability, and energetics of a site-specifically platinated 20-mer DNA duplex. CD spectroscopic and thermal denaturation data revealed that the crosslink alters the structure of the host duplex, consistent with a shift from a B-like to an A-like conformation; lowers its thermal stability by -9°C; and reduces its thermodynamic stability by 6.3 kcal/mol at 25°C, most of which is enthalpic in origin; but it does not alter the two-state melting behavior exhibited by the parent, unmodified duplex, despite the significant crosslinkinduced changes noted above. The energetic consequences of the cis-Pt-GG crosslink are discussed in relation to the structural perturbations it induces in DNA and to how these crosslinkinduced perturbations might modulate protein binding.The chemotherapeutic efficacy of the anticancer drug cisplatin is derived from its ability to bind and crosslink DNA, the major adduct being the cis-Pt-GG intrastrand crosslink (1). Previous crystallographic, NMR, and gel electrophoretic investigations have evaluated the impact of this crosslink on the structure and conformation of the host duplex (1-9). These studies indicate that formation of the cis-Pt-GG crosslink unwinds DNA by 130and bends it by 34-55°in the direction of the major groove. Avery recent crystallographic study revealed that the crosslink can induce formation of an A-form structural subdomain, thereby creating a hybrid DNA duplex with an A-B junction (8). Such cis-Pt-GG-induced alterations in duplex structure have been implicated in the promotion of specific interactions with cellular proteins that contain one or more high mobility group domainsfor example, HMG1, Ixrl, and human upstream-binding factor (hUBF) (8,(10)(11)(12)(13)(14)(15). When bound by such cellular proteins, the cis-Pt-GG sites are shielded from excision repair (11,13,16,17), thereby enhancing the cytotoxic properties of the drug. Unlike the detailed structural information about the major cisplatin-DNA adduct, comparatively little is known about its corresponding energetic consequences. Such thermodynamic data would reveal how the crosslink influences duplex stability, a property that has been implicated in the modulation of protein recognition and binding (18)(19)(20). To address this deficiency, we have used a combination of calorimetric and spectroscopic techniques to characterize the effect of a single cis-Pt-GG intrastrand crosslink on the conformation, thermal stability, and energetics of a 20-mer DNA duplex. The sequences of unmodified (GG20) and modified (cis-Pt-GG20) duplexes examined are depicted in Fig. 1. Inve...

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A d(GpG)‐platinated decanucleotide duplex is kinked

Cited by 108 publications

References 47 publications

Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts

Differences in Conformation and Conformational Dynamics Between Cisplatin and Oxaliplatin DNA Adducts

Structural Transitions of a GG‐Platinated DNA Duplex Induced by pH, Temperature and Box A of High‐Mobility‐Group Protein 1

Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex.

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