DNA damage signaling

There are multiple pathways for p53 induction [161], but the specific mechanism for the activation of p53-mediated responses by cisplatin is still obscure. Details about the DNA-damage signal transduction pathway could be important for the mechanism of cisplatin resistance and must be provided by future research. In contrast, quite a lot is known about the downstream effects of p53. Several of these p53 activities have been implicated in the modulation of cellular sensitivity to cisplatin (Fig. 6). 

Fig. 15.7 The DNA damage-response pathway. DNA damage is sensed by protein kinases. In mammals and in yeast the activation of the ATM kinase and of the DUNl kinase, respectively, is oontrolled by a phosphorylation oasoade, responsive to DNA-damage signals. (ATM is a kinase and the product of the AT gene, the ataxia teiangiectasia gene). p53 is phosphorylated and in humans and yeast p53-P removes the blook at promoters of RNR genes and the nuclear p53R2 IS expressed. (Reproduced from Fig. 2 in ref. 37 with permission of the authors and Nature.)...

Oliver AW, Paul A, Boxall KJ, Barrie SE, Aheme GW, Garrett MD, Mittnacht S, Pearl LH. Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange. EMBO J. 2006 25 3179-3190. 

Lou Z, Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, Manis JP, van Deursen J, Nussenzweig A, Pauli TT, Alt FW, Chen J. MDCl maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell 2006 21 (2) 187-200. 

Ghavidel, A., and Schultz, M. C. (2001). TATA binding protein-associated CK2 transduces DNA damage signals to the RNA polymerase III transcripdonal machinery. Cell 106, 575-584. 

Conserved Core Components in DNA Damage Signal Transduction... 

Descriptors such as sensors, master switches, adaptors/media-tors, and effector kinases suggest an understanding of the mechanism by which DNA damage signal is transduced to regulate cellular processes. 

Zhao H, Halicka HD, Li J, Biela E, Bemiak K, Dobmcki J, Darzynkiewicz Z (2013) DNA damage signaling, impairment of cell cycle progression, and apoptosis triggered by 5-ethynyl-2 -deoxyur-idine incorporated into DNA. Cytometry Part A J Int Soc Anal Clytol 83(ll) 979-988. doi 10.1002/... 

Jowsey, PA., Williams, F.M., Blain, P.G., 2009. DNA damage, signalling and repair after exposure of cells to the sulphur mustard analogue 2-chloroethyl ethyl sulphide. Toxicology 257, 105-112. 

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