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TATA box
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== Clinical significance == === Technology === Many of the studies so far have been performed [[in vitro]], providing only a prediction of what may happen not a real-time representation of what is happening in the [[Cell (biology)|cells]]. Recent studies in 2016 have been done to demonstrate TATA-binding activity [[in vivo]]. Core [[Promoter (genetics)|promoter]]-specific mechanisms for transcription initiation by the canonical TBP/TFIID-dependent basal [[Transcription (biology)|transcription]] machinery has recently been documented [[in vivo]] showing the activation by [[Serum response factor|SRF]]-dependent [[Upstream activating sequence|upstream activating sequence (UAS)]] of the human [[ACTB (gene)|ACTB gene]] involved in TATA-binding.<ref name=":16">{{cite journal | vauthors = Xu M, Gonzalez-Hurtado E, Martinez E | title = Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription | journal = Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | volume = 1859 | issue = 4 | pages = 553β63 | date = April 2016 | pmid = 26824723 | pmc = 4818687 | doi = 10.1016/j.bbagrm.2016.01.005 }}</ref> === Cancer therapy === [[Pharmaceutical companies]] have been designing [[cancer therapy]] [[drug]]s to target [[DNA]] in traditional methods over the years, and have proven to be successful.<ref name=":20">{{cite journal | vauthors = Hurley LH | title = DNA and its associated processes as targets for cancer therapy | journal = Nature Reviews. Cancer | volume = 2 | issue = 3 | pages = 188β200 | date = March 2002 | pmid = 11990855 | doi = 10.1038/nrc749 | s2cid = 24209612 }}</ref> However, the toxicity of these drugs have pushed scientists to explore other processes related to DNA that could be targeted instead. In recent years, a collective effort has been made to find cancer-specific molecular targets, such as protein-DNA complexes, which include the TATA binding motif. Compounds that trap the [[Protein-DNA complex|protein-DNA]] intermediate could result in it being [[Toxicity|toxic]] to the [[Cell (biology)|cell]] once they encounter a [[DNA]] processing event. Example of [[drug]]s that contain such compounds include [[topotecan]], [[SN-38]] ([[topoisomerase I]]), [[doxorubicin]], and [[mitoxantrone]] ([[topoisomerase II]]).<ref name=":20" /> [[Cisplatin]] is a compound that binds [[Covalent bond|covalently]] to adjacent [[guanine]]s in the [[Nucleic acid double helix|major groove]] of [[DNA]], which distorts [[DNA]] to allow access of [[DNA-binding protein]]s in the [[Nucleic acid double helix|minor groove]].<ref name=":20" /> This will destabilize the interaction between the [[TATA-binding protein|TATA-binding protein (TBP)]] to the TATA box. The result is to immobilize the [[TATA-binding protein|TATA-binding protein (TBP)]] on DNA in order to down-regulate [[Transcription (biology)|transcription]] initiation.
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