Genotoxic stress

Antoch M, Kondratov R, Takahashi J (2005) Circadian clock genes as modulators of sensitivity to genotoxic stress. Cell Cycle 4901-907... 

Benhar, M. et al., Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress, Mol. Cell. Biol., 21, 6913, 2001. 

Moreover, overexpression of the same mutants inhibit DNA replication and block the cells at the Gl/S-phase transition (Kim et al, 2005), emphasizing the potential role of nucleolin mobilization. It is therefore highly probable that two different processes help the formation of RPA-nucleolin complexes after a genotoxic stress a post-transcriptional modification of nucleolin that renders the GAR domain of nucleolin accessible to RPA, and its p53-dependent relocalization to the nucleoplasm where a higher amount of RPA is available. Of importance, nucleolin relocalization is transient and lasts far less than replication inhibition (Daniely and Borowiec, 2000). This means that nucleolin-RPA interaction is only an initial event and that other mechanisms account for prolonged replication inhibition. 

Nucleolin could therefore contribute to genome stability in two different ways by modulating the activities of several DNA repair enzymes through physical interaction and by enhancing the translation of some of these proteins after a genotoxic stress (Yang et al., 2002). 

Khurts S, Masutomi K, Delgermaa L, Aral K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (2004) Nucleolin interacts with telomerase. J Biol Chem 279 51508—51515 Kim K, Dimitrova DD, Carta KM, Saxena A, Daras M, Borowiec JA (2005) Novel checkpoint response to genotoxic stress mediated by nucleoUn-repUcation protein a complex formation. Mol Cell Biol... 

Yang C, Maiguel DA, Carrier F (2002) Identification of nucleolin and nucleophosmin as genotoxic stress-responsive RNA-binding proteins. Nucleic Acids Res 30 2251-2260 Yang TH, Tsai WH, Lee YM, Lei HY, Lai MY, Chen DS, Yeh NH, Lee SC (1994) Purification and characterization of nucleolin and its identification as a transcription repressor. Mol Cell Biol 14 6068-6074... 

Col E, Caron C, Chable-Bessia C, Legube G, Gazzeri S, Komatsu Y, Yoshida M, Benkirane M, Trouche D, Khochbin S (2005) HlV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses. Embo J 24 2634-2645... 

Eymin B, Claverie P, Salon C, Leduc C, Col E, Brambilla E, Khochbin S, Gazzeri S (2006) pl4ARF Activates a Tip60-Dependent and p53-Independent ATM/ATR/CHK Pathway in Response to Genotoxic Stress. Mol Cell Biol 26 4339-4350... 

To assess the protective abilities of these chelators, a spontaneously transformed cell line of oligodendroglia origin (OLN 93) was chosen as a model for neural cells. These cells were previously used to demonstrate a remarkable sensitivity to genotoxic stress, culminating in cell death when both divalent iron and H2O2 were added to cells °. ... 

Microbes and metazoans are exposed to a variety of toxic stresses and have evolved appropriate defenses and repair mechanisms. Some of these systems are regulated at the protein level, but others are regulated at the transcriptional level, allowing the development of reporter assays. These transcriptional responses can be used to provide an earlier marker for genotoxin exposure in a whole population of cells, rather than the detection of the endpoints discussed above, in which genotoxic stress leads to fixation of mutations or chromosomal aberrations/damage in a small subpopulation. 

The p53 protein represents a control element that links progress in the cell cycle and smwival of a cell with the effect of genotoxic stress (especially DNA damage). 

The above findings define a proapoptotic signaling pathway involving p73 and c-Abl. Unlike p53, p73 protein levels do not increase following genotoxic stress. Moreover, although c-Abl interacts with p53 in an irradiated cell, it does not phosphorylate p53 but still contributes to radiation-induced G arrest by a p53-dependent mechanism (Yuan et al., 1999). Although p73 is related to p53, p53 alone is the tumor suppressor. p73 protein as yet has not been localized immunohistochemically. 

The purpose of this chapter is to review the types of proteins that interact with or respond to cisplatin-damaged DNA, and to discuss how these proteins can modulate cellular sensitivity to the drug through their participation in various biochemical pathways (Fig. 2). Included are proteins dedicated to dealing with genotoxic stress, such as components of the DNA repair and p53-regulated pathways, but also proteins affected by the DNA structural distortions induced by cisplatin adduct formation, such as transcription factors and architectural proteins. The manner by which such proteins affect the processing of cisplatin-DNA adducts can determine wheth-... 

Amundson, S. A., M. Bittner, P. Meltzer, J. Trent, and A. J. Fornace Jr. (2001). Physiological function as regulation of large transcriptional programs the cellular response to genotoxic stress. Comp. Biochem. Physiol. B, 129 703-710. 

Tinel A, Tschopp J (2004) The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304 843-846 Tomkins J, Usher P, Slade JY, Ince PG, Curtis A, Bushby K, Shaw PJ (1998) Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 9 3967-3970... 

Rotman G, Shiloh Y. ATM a mediator of multiple responses to genotoxic stress. Oncogene 1999 18 6135-6144. 

Holbrook NJ, Fornace AJ, Jr. Response to adversity molecular control of gene activation following genotoxic stress. New Biol. 1991 3(9) 825-833. 

Amundson SA, Myers TG, Fornace AJ, Jr. Roles for p53 in growth arrest and apoptosis putting on the brakes after genotoxic stress. Oncogene. 1998 17(25) 3287-3299. 

Balestrazzi A., Confalonieri M., Macovei A., Dona M., Carbonera D. Genotoxic stress and DNA repair in plants emerging functions and tools for improving crop productivity. Plant Cell Reports 2011 30(3) 287-295. 

Quinones, A. and Rainov, N.G. (2001) Identification of genotoxic stress in human cells by fluorescent monitoring of p53 expression. Mutation Research, 494, 73-85. 

Shackelford, R. E., Kaufmann, W. K., and Paules, R. S. (1999). Cell cycle control, checkpoint mechanisms, and genotoxic stress. Envirm Health Perspect 107(1), 5-24. 

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