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Structure of a polymerase-mediated DNA NHEJ synaptic complex
journal contribution
posted on 2023-06-08, 10:04 authored by Nigel Brissett, Robert S Pitcher, Raquel Juarez, Angel J Picher, Andrew J Green, Timothy R Dafforn, Gavin C Fox, Luis Blanco, Aidan DohertyAidan DohertyNonhomologous 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.
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Publication status
- Published
Journal
ScienceISSN
0028-0836External DOI
Volume
318Page range
456-459Pages
4.0Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
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.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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