XRCC4 (X-ray cross-complementation group 4) and XLF (XRCC4-like factor) are two essential interacting proteins in the human NHEJ (non-homologous end-joining) pathway that repairs DNA DSBs (double-strand breaks). The individual crystal structures show that the dimeric proteins are homologues with protomers containing head domains and helical coiled-coil tails related by approximate two-fold symmetry. Biochemical, mutagenesis, biophysical and structural studies have identified the regions of interaction between the two proteins and suggested models for the XLF–XRCC4 complex. An 8.5 Å (1 Å=0.1 nm) resolution crystal structure of XLF–XRCC4 solved by molecular replacement, together with gel filtration and nano-ESI (nano-electrospray ionization)–MS results, demonstrates that XLF and XRCC4 dimers interact through their head domains and form an alternating left-handed helical structure with polypeptide coiled coils and pseudo-dyads of individual XLF and XRCC4 dimers at right angles to the helical axis.
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October 2011
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Conference Article|
September 21 2011
Non-homologous end-joining partners in a helical dance: structural studies of XLF–XRCC4 interactions
Qian Wu;
Qian Wu
1
*Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
1To whom correspondence should be addressed (email qw222@cam.ac.uk).
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Takashi Ochi;
Takashi Ochi
*Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
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Dijana Matak-Vinkovic;
Dijana Matak-Vinkovic
†University Chemical Laboratory, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.
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Carol V. Robinson;
Carol V. Robinson
‡Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
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Dimitri Y. Chirgadze;
Dimitri Y. Chirgadze
*Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
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Tom L. Blundell
Tom L. Blundell
*Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
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Publisher: Portland Press Ltd
Received:
May 22 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (5): 1387–1392.
Article history
Received:
May 22 2011
Citation
Qian Wu, Takashi Ochi, Dijana Matak-Vinkovic, Carol V. Robinson, Dimitri Y. Chirgadze, Tom L. Blundell; Non-homologous end-joining partners in a helical dance: structural studies of XLF–XRCC4 interactions. Biochem Soc Trans 1 October 2011; 39 (5): 1387–1392. doi: https://doi.org/10.1042/BST0391387
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