Eckpoint abrogation and checkpoint kinase-1 targeting in the therapy of cancer. Br. J. Cancer 98, 523 28. Buscemi, G., Perego, P., Carenini, N., et al. (2004). Activation of ATM and Chk2 kinases in relation for the quantity of DNA strand breaks. Oncogene 23, 7691 700. Buscemi, G., Carlessi, L., Zannini, L., et al. (2006). DNA DS28120313 In Vivo damage-induced cell cycle regulation and function of novel Chk2 phosphoresidues. Mol. Cell. Biol. 26, 7832 845. Buscemi, G., Zannini, L., Fontanella, E., et al. (2009). The shelterin protein TRF2 inhibits Chk2 activity at telomeres within the absence of DNA damage. Curr. Biol. 19, 874 79. Callen, E., Nussenzweig, M.C., and Nussenzweig, A. (2007). Breaking down cell cycle checkpoints and DNA repair for the duration of antigen receptor gene assembly. Oncogene 26, 7759 7764. Canman, C.E. (2003). Checkpoint mediators: relaying signals from DNA strand breaks. Curr. Biol. 13, R488 490. Carlessi, L., Buscemi, G., Fontanella, E., et al. (2010). A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA harm. Biochim. Biophys. Acta 1803, 1213 223. Castedo, M., and Kroemer, G. (2004). Mitotic catastrophe: a special case of apoptosis. J. Soc. Biol. 198, 97 103. Castedo, M., Perfettini, J.L., Roumier, T., et al. (2004). The cell cycle checkpoint kinase Chk2 is really a negative regulator of mitotic catastrophe. Oncogene 23, 4353 4361. Chehab, N.H., Malikzay, A., Appel, M., et al. (2000). Chk2/hCds1 functions as a DNA harm checkpoint in G(1) by stabilizing p53. Genes Dev. 14, 278 288.activities. A lot has been disclosed about CHK2’s function considering that its discovery, but a lot remains to become understood about its activation and, the majority of all, inactivation. Within the subsequent few years, new CHK2 substrates will almost certainly be identified by proteomic approaches and wide screening analyses. Addressing the functional significance of each and every substrate in a lot of cell sorts will probably be a challenging activity that we should conduct, keeping in mind the biological relevance and doable clinical applications. We really need to define these mechanisms and proteins that fine-tune the distinct biological outcomes from the DDR in relation to lesions, cellular kinds, and genetic background. Indeed, a a lot more detailed knowledge of CHK2 activities in human cells in relation to damage kind and extent could enable define the possibility of treating specific tumors by CHK2 activation or inactivation, alone or in combination with other therapies. Especially fascinating may be the possibility of targeting CHK2 in patients with recognized carcinogenic mutations in p53. On the complete we should define the variables as well as the conditions supporting the usage of CHK2 inhibitors to treat cancer inside a personalized manner. In addition, a superior understanding in the response to virus infection or the relationship between DNA