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The Heterochromatic Barrier to DNA Double Strand Break Repair: How to Get the Entry Visa
Southern Alberta Cancer Research Institute, Departments of Biochemistry & Molecular Biology and Oncology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada
Genome Damage and Stability Centre, University of Sussex, Brighton, BN1 9RQ, United Kingdom
* Authors to whom correspondence should be addressed.
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 chromatin surrounding a DSB. Chromatin is broadly divided into open, transcriptionally active, euchromatin (EC) and highly compacted, transcriptionally inert, heterochromatin (HC), although these represent extremes of a spectrum. The HC superstructure restricts both DSB repair and damage response signaling. Moreover, DSBs within HC (HC-DSBs) are rapidly relocalized to the EC-HC interface. The damage response protein kinase, ataxia telangiectasia mutated (ATM), is required for HC-DSB repair but is dispensable for the relocalization of HC-DSBs. It has been proposed that ATM signaling enhances HC relaxation in the DSB vicinity and that this is a prerequisite for HC-DSB repair. Hence, ATM is essential for repair of HC-DSBs. Here, we discuss how HC impacts upon the response to DSBs and how ATM overcomes the barrier that HC poses to repair.
Keywords: DNA non-homologous end-joining; chromatin; heterochromatin; damage response signaling; ataxia telangiectasia mutated; homologous recombination
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Goodarzi, A.A.; Jeggo, P.A. The Heterochromatic Barrier to DNA Double Strand Break Repair: How to Get the Entry Visa. Int. J. Mol. Sci. 2012, 13, 11844-11860.
Goodarzi AA, Jeggo PA. The Heterochromatic Barrier to DNA Double Strand Break Repair: How to Get the Entry Visa. International Journal of Molecular Sciences. 2012; 13(9):11844-11860.
Goodarzi, Aaron A.; Jeggo, Penny A. 2012. "The Heterochromatic Barrier to DNA Double Strand Break Repair: How to Get the Entry Visa." Int. J. Mol. Sci. 13, no. 9: 11844-11860.