TATA Binding Protein Discriminates between Different Lesions on DNA, Resulting in a Transcription Decrease

Abstract

DNA damage recognition by basal transcription factors follows different mechanisms. Using transcriptioncompetition, nitrocellulose filter binding, and DNase I footprinting assays, we show that, although the general transcription factor TFIIH is able to target any kind of lesion which can be repaired by the nucleotide excision repair pathway, TATA binding protein (TBP)-TFIID is more selective in damage recognition. Only genotoxic agents which are able to induce kinked DNA structures similar to the one for the TATA box in its TBP complex are recognized. Indeed, DNase I footprinting patterns reveal that TBP protects equally 4 nucleotides upstream and 6 nucleotides downstream from the A-T (at position ؊29 of the noncoding strand) of the adenovirus major late promoter and from the G-G of a cisplatin-induced 1,2-d(GpG) cross-link. Together, our results may partially explain differences in transcription inhibition rates following DNA damage.Many carcinogens and antitumor agents structurally modify DNA, often at specific DNA sequences, with as a consequence the disturbance of mechanisms which govern cell life. Following DNA damage, one observes cell cycle arrests in G 2 /M and G 1 phases and a decrease in the rate of transcription. Investigations aimed at elucidating how cells respond to DNA damage evidenced a transcriptionally connected subpathway of DNA repair, called nucleotide excision repair (NER), in which lesions in transcribed genes were preferentially repaired (4,28). This connection between the two mechanisms was further and definitively established when it was demonstrated that the multiprotein complex TFIIH, essential for protein-encoding gene transcription, was also fundamental for NER (for reviews, see references 16 and 36).One of the first steps of any repair process is recognition of the damage, and thus, significant studies have been devoted to identifying proteins able to bind specifically to cisplatin-or UV-induced lesions (for a review, see reference 5). In an effort to understand how TFIIH shuttles between the transcription template and the DNA lesion, we surprisingly demonstrated that TATA binding protein (TBP)-TFIID, another essential basal transcription factor which normally recognizes the TATA box sequence located 30 bp upstream from the transcription start site, also interacts with damaged DNA (41).Before trying to understand the putative role of TBP in DNA repair, we considered it worthwhile to expand our investigations examining the connection between these two essential transcription components, TFIIH and TFIID, and several damaged DNAs. Seven different drugs ( Fig. 1 and Table 1) which bind covalently to DNA were chosen. The platinum derivatives form mono-or bifunctional adducts with DNA. First, the diethylenetriaminedichloroplatinum(II) derivative (Dien) (24) was chosen for its ability to form a monofunctional adduct recognized by the NER pathway in bacteria (2). Cisplatin (CDDP), transplatin (TDDP), and dachplatin (Dach) were used for their capacity to induce monofunctional adducts which ...

The Antileukemia Drug 2-Chloro-2′-deoxyadenosine: An Intrinsic Transcriptional Antagonist

“…cis-Diamminedichloroplatinum (cisplatin)-, UV-, and N-2-acetylaminofluorene-damaged DNA are all very effective competitor binding sites for TBP because of distortion or kinks introduced into DNA molecules by these forms of damage (Vichi et al, 1997;Coin et al, 1998). Cisplatin adducts situated near a TATA box enhanced TBP binding to its consensus sequence; interestingly, however, they also caused a much slower dissociation rate (Cohen et al, 2000) similar to our finding with CldAMP residues.…”

The VirD2 pilot protein of Agrobacterium -transferred DNA interacts with the TATA box-binding protein and a nuclear protein kinase in plants

“…VirD2 is thought to target the T-complex to free 3Ј DNA ends of nicks and gaps in chromatin domains, where the dsDNA is melted (25). Recent demonstration (37)(38) that the TBP can bind to lesions in the DNA to initiate transcription-coupled repair has raised the question whether TBP can recruit the VirD2 protein. First, we have analyzed the interaction of VirD2 with Arabidopsis TBP in vitro.…”

“…CAK2Ms isolated by immunoprecipitation phosphorylates cyclin-dependent kinase (CDK2) and the C-terminal domain (CTD) of RNA polymerase II largest subunit, which serves as a TBP-binding platform. Remarkable functional conservation of TBP and CDK-activating protein kinase (CAK2) orthologs in eukaryotes suggests that these nuclear VirD2-binding factors provide a link between T-DNA integration and transcriptioncoupled repair (37)(38).…”

Solution Structures of a DNA Dodecamer Duplex with and without a Cisplatin 1,2-d(GG) Intrastrand Cross-Link: Comparison with the Same DNA Duplex Containing an Oxaliplatin 1,2-d(GG) Intrastrand Cross-Link,

“…The mechanism(s) by which the binding of these proteins to Pt-DNA adducts influences the cytotoxic response is not known but has been postulated to involve shielding of the adducts from DNA repair and tolerance mechanisms (16)(17)(18)(19), activation of signaling pathways leading to cell cycle arrest or apoptosis, and/or hijacking of transcription factors needed for DNA replication or cell division (15,20). The binding specificity has been determined for only a few of these proteins, but where it has been studied, these proteins bind to CP-GG adducts with higher affinity than to OX-GG adducts (14,15,21). Finally, translesion DNA polymerases such as pol β and pol η have been shown to bypass OX-GG adducts with higher efficiency than CP-GG adducts (19,22,23), which might contribute to the differences in CP and OX mutagenicity.…”