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Molecular basis for DNA strand displacement by NHEJ repair polymerases

DOI: 10.1093/nar/gkv965 DOI Help
PMID: 26405198 PMID Help

Authors: Edward J. Bartlett (Genome Damage and Stability Centre, University of Sussex) , Nigel Brissett (Genome Damage and Stability Centre, University of Sussex) , Przemyslaw Plocinski (Genome Damage and Stability Centre, University of Sussex) , Tom Carlberg (Genome Damage and Stability Centre, University of Sussex) , Aidan J. Doherty (Genome Damage and Stability Centre, University of Sussex)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research

State: Published (Approved)
Published: September 2015

Open Access Open Access

Abstract: The non-homologous end-joining (NHEJ) pathway repairs DNA double-strand breaks (DSBs) in all domains of life. Archaea and bacteria utilize a conserved set of multifunctional proteins in a pathway termed Archaeo-Prokaryotic (AP) NHEJ that facilitates DSB repair. Archaeal NHEJ polymerases (Pol) are capable of strand displacement synthesis, whilst filling DNA gaps or partially annealed DNA ends, which can give rise to unligatable intermediates. However, an associated NHEJ phosphoesterase (PE) resects these products to ensure that efficient ligation occurs. Here, we describe the crystal structures of these archaeal (Methanocella paludicola) NHEJ nuclease and polymerase enzymes, demonstrating their strict structural conservation with their bacterial NHEJ counterparts. Structural analysis, in conjunction with biochemical studies, has uncovered the molecular basis for DNA strand displacement synthesis in AP-NHEJ, revealing the mechanisms that enable Pol and PE to displace annealed bases to facilitate their respective roles in DSB repair.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 24/10/2015 20:17

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