coincident in vitro analysis of dna-pk-dependent and -independent nonhomologous end joining重合的体外分析dna-pk-dependent和独立nonhomologous加入结束.pdfVIP

SAGE-Hindawi Access to Research Journal of Nucleic Acids Volume 2010, Article ID 823917, 11 pages doi:10.4061/2010/823917 Research Article Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining Cynthia L. Hendrickson,1, 2 Shubhadeep Purkayastha,1 Elzbieta Pastwa,3 Ronald D. Neumann,1 and Thomas A. Winters1 1 Radiology Imaging Sciences Department, Nuclear Medicine Section, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA 2 Applied Biosystems, Advanced Genetic Applications, 500 Cummiing Center, Suite 2450, Beverly, MA 01915, USA 3 Molecular Genetics Department, Medical University of Lodz, Lodz 92-215, Poland Correspondence should be addressed to Thomas A. Winters, twinters@ Received 15 May 2010; Accepted 6 June 2010 Academic Editor: Ashis Basu Copyright © 2010 Cynthia L. Hendrickson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In mammalian cells, DNA double-strand breaks (DSBs) are primarily repaired by nonhomologous end joining (NHEJ). The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA- dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that mediate DSB end joining. However, recent studies show that additional DNA-PK-independent NHEJ pathways also exist. Unfortunately, t