Engineering a DNA damage response without DNA damage.docVIP

Minireview Engineering a DNA damage response without DNA damage ManTek Yeung*? and Daniel Durocher*? Addresses: *Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University Avenue, Toronto, ON, M5G 1X5 Canada. ?Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8 Canada. Correspondence: Daniel Durocher. Email: durocher@mshri.on.ca Published: 28 July 2008 Genome Biology 2008, 9:227 (doi:10.1186/gb-2008-9-7-227) The electronic version of this article is the complete one and can be found online at /2008/9/7/227 ? 2008 BioMed Central Ltd Abstract Recent work has achieved the feat of activating the DNA damage checkpoint in the absence of DNA damage, revealing the importance of protein-chromatin associations for the activation, amplification and maintenance of the DNA damage response. Detecting and repairing DNA damage is critical for the faithful transmission of genetic information. In response to DNA lesions, cells activate a complex cellular response, which at its core consists of a signal transduction cascade controlled by members of the PI(3) kinase-like kinase (PIKK) family [1,2]. This signaling cascade, often referred to as the DNA damage checkpoint, primarily aims to co- ordinate DNA repair with the arrest or slowing down of the cell cycle (the checkpoint). Failure to detect and repair DNA damage can lead to cell death or to genome aberrations that can promote the development of cancer. modifications. Why is DNA damage signaling organized this way? Recent work published by Evi Soutoglou and Tom Misteli in Science [5] and by David Toczyski and colleagues in Molecular Cell (Bonilla et al. [6]) address this critical question by reverse-engineering the DNA damage response, to spectacular effect. Recruitment of checkpoint proteins to DNA lesions Soutoglou and Misteli [5] and Bonilla et al. [6] investigate DNA damage sig