Activation of DNA binding

Post-translational covalent modification of DNA-binding proteins is a mechanism commonly employed among eucaryotes to control the activity of DNA-binding proteins. 

The principal mechanisms for the control of the DNA-binding activity of DNA-binding proteins have been presented in section 1.3.2. 

P. A. Baeuerle and D. Baltimore, Activation of DNA-Binding Activity in an Apparently Cytoplasmic Precursor of the NF-kappa B Transcription Factor, Cell 53 (1988) 211-217. 

AdoMet can interact with Dam in the absence of DNA. The two successive steps of the activation of DNA binding by AdoMet and the conformational change induced by the interaction with the specific sequence suggest that the catalytic mechanism of Dam is, unlike M EcoRI, closer to that of type I R—M systems such as EcoBI and EcoKI. 

Another class of DNA-binding proteins are the polymerases. These have a nonspecific interaction with DNA because the same protein acts on all DNA sequences. DNA polymerase performs the dual function of DNA repHcation, in which nucleotides are added to a growing strand of DNA, and acts as a nuclease to remove mismatched nucleotides. The domain that performs the nuclease activity has an a/P-stmcture, a deep cleft that can accommodate double-stranded DNA, and a positively charged surface complementary to the phosphate groups of DNA. The smaller domain contains the exonuclease active site at a smaller cleft on the surface which can accommodate a single nucleotide. 

Sarge, K.D., Murphy, S.P., Morimoto, R.l. (1993). Activation of heat shock gene transcription by heat shock factor 1 involves oligomenzation, acquisition of DNA binding activity, and nuclear localization and can occur in the absence of stress. Mol. Cell. Biol. 13. 1392-1407. 

SAINZ, M., GROTEWOLD, E., CHANDLER, V., Evidence for direct activation on an anthocyanin promoter by the maize Cl protein and comparison of DNA binding by related Myb-domain proteins, Plant Cell, 1997,9, 611-625. 

In this review, we present an introduction to the theory, and exemplify the wide range of problems that can be addressed with some illustrative results from our work in the field of ah initio drug design. The problems addressed are those of activation and DNA binding of the antitumor drug cis-platin (PtCl2(NH3)2), and basic spectrometric data from a family of drugs known as psoralens. 

SoxR, OxyR Fur LAC9 Acel —rather uniform results showing activation -de-repression of genes that are under the control of Fur —attenuated DNA-binding in vitro —inhibition of DNA-binding in yeast... 

NF-kB AP-1 Spl, Egr-1 (zinc finger TFs) VDR, RXR (nuclear hormone R) PPARy NFAT HSFs p53 HIF-1 -activation in resting cells, low level RNI -inhibition in stimulated cells, high level RNI -activation in unstimulated cells, low level RNI -inhibition in activated cells -rather uniform inhibition -activation if Spl de-represses the e.g. TNFa promoter -inhibition of DNA-binding and reporter activity -activation at low level RNI -inhibition at high level RN I —inhibition in activated N K cells -activation (HSP70 expression) —activation (for details see below) -activation under normoxia (for details see below) -inhibition under hypoxia... 

Hollenberg, S.M., Giguere, V, Segui, P. and Evans, R.M. (1987). Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell 49 39-46. 

---