Structure of a polymerase-mediated DNA NHEJ synaptic complex

Brissett, Nigel C, Pitcher, Robert S, Juarez, Raquel, Picher, Angel J, Green, Andrew J, Dafforn, Timothy R, Fox, Gavin C, Blanco, Luis and Doherty, Aidan J (2007) Structure of a polymerase-mediated DNA NHEJ synaptic complex. Science, 318. pp. 456-459. ISSN 0028-0836

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Abstract

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.

Item Type: Article
Additional Information: AD directed research and was the corresponding author. This paper describes how non homologous DNA repair polymerases can promote the association of the ends of a double-strand break. Data is presented revealing a molecular snapshot of a DNA break being held together via a dimeric arrangement of polymerases.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Nigel Brissett
Date Deposited: 06 Feb 2012 21:28
Last Modified: 03 Apr 2012 11:33
URI: http://sro.sussex.ac.uk/id/eprint/31343
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