Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 19 October 2007:
Vol. 318. no. 5849, pp. 456 - 459
DOI: 10.1126/science.1145112
Prev | Table of Contents | Next

Reports

Structure of a NHEJ Polymerase-Mediated DNA Synaptic Complex

Nigel C. Brissett,1* Robert S. Pitcher,1* Raquel Juarez,2 Angel J. Picher,2 Andrew J. Green,1 Timothy R. Dafforn,3 Gavin C. Fox,4 Luis Blanco,2{dagger} Aidan J. Doherty1{dagger}

Nonhomologous end joining (NHEJ) is a critical DNA double-strand break (DSB) repair pathway required to maintain genome stability. Many prokaryotes possess a minimalist NHEJ apparatus required to repair DSBs during stationary phase, composed of two conserved core proteins, Ku and ligase D (LigD). The crystal structure of Mycobacterium tuberculosis polymerase domain of LigD mediating the synapsis of two noncomplementary DNA ends revealed a variety of interactions, including microhomology base pairing, mismatched and flipped-out bases, and 3' termini forming hairpin-like ends. Biochemical and biophysical studies confirmed that polymerase-induced end synapsis also occurs in solution. We propose that this DNA synaptic structure reflects an intermediate bridging stage of the NHEJ process, before end processing and ligation, with both the polymerase and the DNA sequence playing pivotal roles in determining the sequential order of synapsis and remodeling before end joining.

1 Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.
2 Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.
3 Department of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
4 European Synchrotron Radiation Facility, LLS-BM16, Grenoble Cedex 9, France.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: lblanco{at}cbm.uam.es (L.B.); ajd21{at}sussex.ac.uk (A.J.D.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
End-bridging is required for pol {micro} to efficiently promote repair of noncomplementary ends by nonhomologous end joining.
B. J. Davis, J. M. Havener, and D. A. Ramsden (2008)
Nucleic Acids Res. 36, 3085-3094
   Abstract »    Full Text »    PDF »
Bacterial Nonhomologous End Joining Ligases Preferentially Seal Breaks with a 3'-OH Monoribonucleotide.
H. Zhu and S. Shuman (2008)
J. Biol. Chem. 283, 8331-8339
   Abstract »    Full Text »    PDF »
Mechanistic flexibility as a conserved theme across 3 billion years of nonhomologous DNA end-joining.
J. Gu and M. R. Lieber (2008)
Genes & Dev. 22, 411-415
   Full Text »    PDF »
The pathways and outcomes of mycobacterial NHEJ depend on the structure of the broken DNA ends.
J. Aniukwu, M. S. Glickman, and S. Shuman (2008)
Genes & Dev. 22, 512-527
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)