Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The overexpression of DNA polymerase beta (beta-pol) has been identified in lots of human cancers, but the mechanism has seldom been investigated. Telomerase transcriptional element-interacting factor (TEIF) can bind to hTERT promoter, stimulating its transcription and telomerase activities. Here, we report that TEIF could also enhance the expression of beta-pol at transcription level. TEIF could specifically activate transcription of beta-pol promoter, but not that of DNA polymerase alpha or delta promoter. The responsible sequences for binding of TEIF were revealed as GC-rich elements dispersing from +19 to -29 nt of beta-pol promoter, which due to mutations caused decreasing in binding of TEIF and apparent losing of transactivation activity. The in vivo interaction between TEIF and beta-pol promoter was identified by chromatin immunoprecipitation assay. Besides, ectopic expression of TEIF in HeLa cells could upregulate both levels of endogenous beta-pol mRNA and protein, and consequently increases resistance to the oxidative stress of H2O2. The data may provide new clue to the elucidation of beta-pol overexpression in cancers and also a functional link between beta-pol and telomerase.
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PMID:Transcriptional upregulation of DNA polymerase beta by TEIF. 1596 46

In a previous study, we demonstrated that telomerase transcriptional elements-interacting factor (TEIF) could up-regulate the expression of telomerase and DNA polymerase beta, increasing resistance to genotoxic agents. Here, we further report that TEIF can be stimulated by DNA damage and we have identified a cluster of repeated polypyrimidine tracts in the promoter of TEIF, which mediate both its basal transcription and its response to genotoxic agents. These polypyrimidine tracts are arranged in three types of repeating units and in each of these units there are 14 bp length tandem sequences, which are repeated three times. These sequences are also characteristically separated by an 11 bp interval sequence. Among these units, one type (5'-CCCCCCCATCCCCG-3') has been found to be involved in the transcriptional regulation of TEIF. At the same time, PTB1 (polypyrimidine tract-binding protein 1) has been shown to repress TEIF expression through interaction with this element. Up-regulation of TEIF may be achieved by PTB1 suppression that is induced by DNA damage, or by an olignucleotide decoy, which mediates reversal of suppression. This study provides new insight into the mechanism through which TEIF is involved in DNA damage response, together with insight into the role of polypyrimidine tracts in transcription regulation.
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PMID:A cluster of polypyrimidine tracts is involved in the transcription regulation of telomerase transcriptional elements-interacting factor. 1921 9