Abstract
The ability of cells to maintain their genomic integrity is essential to the prevention of cancer development. Double-strand breaks (DSBs), the most harmful type of lesion to DNA, are sensed by ataxia-telangiectasia mutated (ATM) protein in association with the MRE11-RAD50-NBS1 complex. The ATM kinase, which is mutated in ataxia-telangiectasia disorder, is a crucial guardian of genomic integrity. Its activation in response to DSBs orchestrates the DNA damage response (DDR) by phosphorylating a plethora of substrates that modulate processes such as DNA repair and cell cycle checkpoints. In this chapter we focus on the molecular mechanisms involved in ATM activation and cell cycle control in response to DSBs and, specifically, on the cross-talk between ATM and retinoblastoma protein (pRb) phosphorylation.
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Acknowledgments
This study was supported by grants from the Spanish Ministry of Education and Science SAF-2009-13093, BFU2010-19119 and BFU2010-22149 the Fondo de Investigación Sanitaria and the Instituto de Salud Carlos III (PI080400 and PS09/01789) (FEDER FOUNDS). We thank the Catalan Government (Generalitat de Catalunya) for supporting the research groups (2009/SGR00853). 610RT0405 from Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (CYTED). We thank the University of Barcelona Language Services for revising the manuscript.
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Pizarro, J.G. et al. (2012). Cell Cycle Control by Ataxia Telangiectasia Mutated Protein Through Regulating Retinoblastoma Protein Phosphorylation. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 8. Tumors of the Central Nervous System, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4213-0_11
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DOI: https://doi.org/10.1007/978-94-007-4213-0_11
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