Journal
NANOMEDICINE
Volume 3, Issue 1, Pages 93-105Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/17435889.3.1.93
Keywords
DNA-dependent protein kinase; DNA recombination; DNA repair; gene therapy; ionizing radiation; nonhomologous end joining; protein labeling; quantum dots; super-resolution microscopy
Funding
- NCI NIH HHS [R01 CA098239-04, R01 CA098239, 5R01CA098239] Funding Source: Medline
- NEI NIH HHS [1PN2EY018244, PN2 EY018244-01, PN2 EY018244] Funding Source: Medline
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The mammalian nucleus is filled with self-organizing, nanometer-scale nucleoprotein machines that carry out DNA replication, RNA biogenesis and DNA repair. We discuss, as a model, the nonhomologous end-joining (NHEJ) machine, which repairs DNA double-strand breaks. The NHEJ machine consists of six core polypepticles and 10-20 ancillary polypepticles. A full understanding of its design principles will require measuring the behavior of single NHEJ complexes in living cells, using a Nano Toolbox that includes bright, stable, biocompatible fluorophores, efficient protein and nucleic acid-tagging strategies, and sensitive, high-resolution imaging methods. Taking inspiration from natural examples, it might be possible to adapt and redesign the NHEJ machine to precisely correct mutations responsible for common human diseases, such as K-ras in lung cancer or human papillornavirus E6 and E7 genes in cervical and oral cancers.
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