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Int. J. Mol. Sci. 2012, 13, 11844-11860; doi:10.3390/ijms130911844 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review The Heterochromatic Barrier to DNA Double Strand Break Repair: How to Get the Entry Visa Aaron A. Goodarzi 1,* and Penny A. Jeggo 2,* 1 Southern Alberta Cancer Research Institute, Departments of Biochemistry Molecular Biology and Oncology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada 2 Genome Damage and Stability Centre, University of Sussex, Brighton, BN1 9RQ, United Kingdom * Author to whom correspondence should be addressed; E-Mails: a.goodarzi@ucalgary.ca (A.A.G.); p.a.jeggo@sussex.ac.uk (P.A.J.); Tel.: +1-4032204896 (A.A.G.); +4-41273678482 (P.A.J.); Fax: +1-4032108135 (A.A.G.); +4-41273678121 (P.A.J.). Received: 17 August 2012; in revised form: 13 September 2012 / Accepted: 14 September 2012 / Published: 19 September 2012 Abstract: Over recent decades, a deep understanding of pathways that repair DNA double strand breaks (DSB) has been gained from biochemical, structural, biophysical and cellular studies. DNA non-homologous end-joining (NHEJ) and homologous recombination (HR) represent the two major DSB repair pathways, and both processes are now well understood. Recent work has demonstrated that the chromatin environment at a DSB significantly impacts upon DSB repair and that, moreover, dramatic modifications arise in the