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Summary
February 2008, Vol. 3, No. 1, Pages 93-105
(doi:10.2217/17435889.3.1.93)
Understanding and re-engineering nucleoprotein machines to cure human disease William Dynan 1 , Yoshihiko Takeda2, David Roth3 & Gang Bao4*1Institute of Molecular Medicine & Genetics, Medical College of Georgia, Augusta, GA 30912, USA. wdynan@mcg.edu 2Institute of Molecular Medicine & Genetics, Medical College of Georgia, Augusta, GA 30912, USA. ytakeda@meg.edu 3The Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. roth@saturn.med.nyu.edu 4Georgia Institute of Technology and Emory University, Department of Biomedical Engineering, Atlanta, GA 30332, USA. gang.bao@bme.gatech.edu † Author for correspondence *To whom correspondence may also be addressed 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 polypeptides and 10–20 ancillary polypeptides. 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 papillomavirus E6 and E7 genes in cervical and oral cancers.
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