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Molecular basis for DNA strand displacement by NHEJ repair polymerases

journal contribution
posted on 2023-06-09, 00:00 authored by Edward J Bartlett, Nigel Brissett, Przemyslaw Plocinski, Tom Carlberg, Aidan DohertyAidan Doherty
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nucleic Acids Research

ISSN

0305-1048

Publisher

Oxford University Press

Issue

5

Volume

44

Page range

2173-2186

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-15

First Open Access (FOA) Date

2016-01-15

First Compliant Deposit (FCD) Date

2016-01-15

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