12周文献 DNA双链修复.pdfVIP

LETTER doi:10.1038/nature18643 Sliding sleeves of XRCC4–XLF bridge DNA and connect fragments of broken DNA 1 1 1 1 1 2 Ineke Brouwer *, Gerrit Sitters *†, Andrea Candelli †, Stephanie J. Heerema †, Iddo Heller , Abinadabe J. de Melo , 2 2 2 1 1 Hongshan Zhang , Davide Normanno , Mauro Modesti §, Erwin J. G. Peterman § Gijs J. L. Wuite § Non-homologous end joining (NHEJ) is the primary pathway us to investigate the bringing and holding together of DNA fragments for repairing DNA double-strand breaks (DSBs) in mammalian by human XRCC4 and XLF, key intermediate steps in NHEJ. 1 cells . Such breaks are formed, for example, during gene-segment First, we studied the interaction of fluorescently labelled XLF rearrangements in the adaptive immune system or by cancer and XRCC4 (Extended Data Figs 1–3) on DNA held taut by two therapeutic agents. Although the core components of the NHEJ optically trapped microspheres (Fig. 1). Such experiments show that machinery are known, it has remained difficult to assess the both proteins bind to end-occluded dsDNA but not to stretched specific roles of these components and the dynamics of bringing and holding the fragments of broken DNA together. The structurally a b c