DNA double-strand break repair: from mechanistic understanding to cancer treatment.

@article{citeulike:1897160, abstract = {Accurate repair of DNA double-strand breaks is essential to life. Indeed, defective DNA double-strand break repair can lead to toxicity and large scale sequence rearrangements that cause cancer and promote premature aging. Here, we highlight the two major repair systems for handling DNA double-strand breaks: homologous recombination and non-homologous end joining. To clarify recombination mechanisms, we present animations that illustrate DNA strand movements. In addition to describing how these pathways operate, we also describe why appropriate pathway choice is critical to genomic stability, and we summarize key pathway control features related to cell cycle checkpoint and apoptosis signaling. Importantly, recent progress in delineating the effects of specific defects in repair and checkpoint control has helped to explain several disease phenotypes, including cancer and premature aging. Improved understanding of these pathways has also sparked development of novel chemotherapeutic strategies that kill tumors with increased specificity and efficacy. This review aims to provide a foundational understanding of how the homologous recombination and non-homologous end joining pathways operate, and to demonstrate how a better understanding of these processes has advanced both our understanding of the underlying causes of cancer and our ability to innovate novel cancer treatment strategies.}, address = {Radiation Oncology \& Biology, University of Oxford, Oxford OX3 7LJ, UK.}, author = {Helleday, T. and Lo, J. and van Gent, D. C. and Engelward, B. P. }, citeulike-article-id = {1897160}, doi = {10.1016/j.dnarep.2007.02.006}, issn = {1568-7864}, journal = {DNA Repair (Amst)}, keywords = {dna, repair}, month = {July}, number = {7}, pages = {923--935}, posted-at = {2008-05-08 22:47:04}, priority = {2}, title = {DNA double-strand break repair: from mechanistic understanding to cancer treatment.}, url = {http://dx.doi.org/10.1016/j.dnarep.2007.02.006}, volume = {6}, year = {2007} }

TY - JOUR ID - citeulike:1897160 L3 - citeulike-article-id:1897160 TI - DNA double-strand break repair: from mechanistic understanding to cancer treatment. JF - DNA Repair (Amst) VL - 6 IS - 7 SP - 923 EP - 935 AD - Radiation Oncology & Biology, University of Oxford, Oxford OX3 7LJ, UK. SN - 1568-7864 N2 - Accurate repair of DNA double-strand breaks is essential to life. Indeed, defective DNA double-strand break repair can lead to toxicity and large scale sequence rearrangements that cause cancer and promote premature aging. Here, we highlight the two major repair systems for handling DNA double-strand breaks: homologous recombination and non-homologous end joining. To clarify recombination mechanisms, we present animations that illustrate DNA strand movements. In addition to describing how these pathways operate, we also describe why appropriate pathway choice is critical to genomic stability, and we summarize key pathway control features related to cell cycle checkpoint and apoptosis signaling. Importantly, recent progress in delineating the effects of specific defects in repair and checkpoint control has helped to explain several disease phenotypes, including cancer and premature aging. Improved understanding of these pathways has also sparked development of novel chemotherapeutic strategies that kill tumors with increased specificity and efficacy. This review aims to provide a foundational understanding of how the homologous recombination and non-homologous end joining pathways operate, and to demonstrate how a better understanding of these processes has advanced both our understanding of the underlying causes of cancer and our ability to innovate novel cancer treatment strategies. KW - dna KW - repair AU - Helleday, T AU - Lo, J AU - van Gent, DC AU - Engelward, BP PY - 2007/07/01/ UR - http://dx.doi.org/10.1016/j.dnarep.2007.02.006 ER -