Analysis of HMG protein binding to DNA modified with the anticancer drug cisplatin

Cryer, Jonathan E.; Johnson, Steven W.; Engelsberg, Beatrice N.; Billings, Paul C.

doi:10.1007/s002800050465

Cited by 8 publications

(5 citation statements)

References 20 publications

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“…For instance, it has recently been shown that p53 binds to cisplatin damaged DNA [127]. Similarly, two structural chromatin components, high mobility group proteins (HMG) [29,34,43,51,128,129] and histone H1 [130], exhibit increased affinity to DNA modified with cisplatin (Fig. (2B)).…”

Section: Cisplatinmentioning

confidence: 96%

Transcription Factors As Targets for DNA-Interacting Drugs

Gniazdowski¹,

Denny²,

Nelson³

et al. 2003

CMC

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Gene expression, both tissue specific or inducible, is controlled at the level of transcription by various transcription factors interacting with specific sequences of DNA. Anticancer drugs and other potential therapeutic agents alter interactions of regulatory proteins with DNA by a variety of different mechanisms. The main ones, considered in the review, are: i) competition for the transcription factor DNA binding sequences by drugs that interact non-covalently with DNA (e.g. anthracyclines, acridines, actinomycin D, pyrrole antibiotics and their polyamide derivatives); ii) covalent modifications of DNA by alkylating agents (e.g. nitrogen mustards, cisplatin) that prevent transcription factors from recognizing their specific sequences, or that result in multiple "unnatural" binding sites in DNA which hijack the transcription factors, thus decreasing their availability in the nucleus; iii) competition with binding sites on the transcription factors by synthetic oligonucleotides or peptide nucleic acids in an antigene strategy. The latter compounds may also compete for binding sites on regulatory proteins, acting as decoys to lower their active concentration in the cell. In this review, we have summarized recent advances which have been made towards understanding the above mechanisms by which small molecules interfere with the function of transcription factors.

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Section: Cisplatinmentioning

confidence: 96%

Transcription Factors As Targets for DNA-Interacting Drugs

Gniazdowski¹,

Denny²,

Nelson³

et al. 2003

CMC

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“…Nevertheless, mismatch correction deficiency is correlated with the cisplatin tolerance of cells, and it appears that the most likely form of interference in i o is replication-associated physical competition between mismatch recognition factors and other lesion-recognizing factors, including proteins containing HMG (high-mobility-group)-box motifs [145][146][147][148]. It is not clear, however, how mismatch repair proteins, HMG-box proteins or other cellular factors can modulate NER, but it is possible that they either facilitate lesion processing by attracting repair factors or inhibit correction by shielding the adducts.…”

Section: Cis-platinummentioning

confidence: 99%

Recognition of DNA alterations by the mismatch repair system

Marra¹,

Schär²

1999

Biochem. J.

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Misincorporation of non-complementary bases by DNA polymerases is a major source of the occurrence of promutagenic base-pairing errors during DNA replication or repair. Base-base mismatches or loops of extra bases can arise which, if left unrepaired, will generate point or frameshift mutations respectively. To counteract this mutagenic potential, organisms have developed a number of elaborate surveillance and repair strategies which co-operate to maintain the integrity of their genomes. An important replication-associated correction function is provided by the post-replicative mismatch repair system. This system is highly conserved among species and appears to be the major pathway for strand-specific elimination of base-base mispairs and short insertion/deletion loops (IDLs), not only during DNA replication, but also in intermediates of homologous recombination. The efficiency of repair of different base-pairing errors in the DNA varies, and appears to depend on multiple factors, such as the physical structure of the mismatch and sequence context effects. These structural aspects of mismatch repair are poorly understood. In contrast, remarkable progress in understanding the biochemical role of error-recognition proteins has been made in the recent past. In eukaryotes, two heterodimers consisting of MutS-homologous proteins have been shown to share the function of mismatch recognition in vivo and in vitro. A first MutS homologue, MSH2, is present in both heterodimers, and the specificity for mismatch recognition is dictated by its association with either of two other MutS homologues: MSH6 for recognition of base-base mismatches and small IDLs, or MSH3 for recognition of IDLs only. Mismatch repair deficiency in cells can arise through mutation, transcriptional silencing or as a result of imbalanced expression of these genes.

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“…The possibility that cellular proteins may shield 1,2-intrastrand cisplatin-DNA crosslinks from NER enzymes has been raised previously (6,12,24). Cellular factors that bind to the structural distortions caused by 1,2-intrastrand d(GpG)-and d(ApG)-cisplatin crosslinks have been detected in human cell extracts (12,(34)(35)(36)(37), notably several proteins containing HMG-box motifs (38)(39)(40)(41). None of the HMG-box proteins tested were able to bind a 1,3-intrastrand d(GpTpG)-cisplatin crosslink.…”

Section: Differential Nucleotide Excision Repair Of 12 and 13-intramentioning

confidence: 99%

Differential human nucleotide excision repair of paired and mispaired cisplatin-DNA adducts

Moggs¹,

Szymkowski

Yamada

et al. 1997

Nucleic Acids Research

127

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In order to understand the action of the chemotherapeutic drug cisplatin, it is necessary to determine why some types of cisplatin-DNA intrastrand crosslinks are repaired better than others. Using cell extracts and circular duplex DNA, we compared nucleotide excision repair of uniquely placed 1,2-GG, 1,2-AG, and 1,3-GTG cisplatin-crosslinks, and a 2-acetylaminofluorene lesion. The 1,3 crosslink and the acetylaminofluorene lesion were repaired by normal cell extracts approximately 15-20 fold better than the 1,2 crosslinks. No evidence was found for selective shielding of 1,2 cisplatin crosslinks from repair by cellular proteins. Fractionation of cell extracts to remove putative shielding proteins did not improve repair of the 1,2-GG crosslink, and cell extracts did not selectively inhibit access of UvrABC incision nuclease to 1,2-GG crosslinks. The poorer repair of 1,2 crosslinks in comparison to the 1,3 crosslink is more likely a consequence of different structural alterations of the DNA helix. In support of this, a 1,2-GG-cisplatin crosslink was much better repaired when it was opposite one or two non-complementary thymines. Extracts from cells defective in the hMutSalpha mismatch binding activity also showed preferential repair of the 1,3 crosslink over the 1,2 crosslink, and increased repair of the 1,2 adduct when opposite thymines, showing that hMutSalphais not involved in the differential NER of these substrates in vitro. Mismatched cisplatin adducts could arise by translesion DNA synthesis, and improved repair of such adducts could promote cisplatin-induced mutagenesis in some cases.

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Analysis of HMG protein binding to DNA modified with the anticancer drug cisplatin

Cited by 8 publications

References 20 publications

Transcription Factors As Targets for DNA-Interacting Drugs

Transcription Factors As Targets for DNA-Interacting Drugs

Recognition of DNA alterations by the mismatch repair system

Differential human nucleotide excision repair of paired and mispaired cisplatin-DNA adducts

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