Mechanistic insights into Lhr helicase function in DNA repair.

Ryan Buckley, Kevin Kramm, Christopher D. O. Cooper, Dina Grohmann, Edward L Bolt

Research output: Contribution to journalArticle

Abstract

The DNA helicase Large helicase-related (Lhr) is present throughout archaea, including in the Asgard and Nanoarchaea, and has homologues in bacteria and eukaryotes. It is thought to function in DNA repair but in a context that is not known. Our data show that archaeal Lhr preferentially targets DNA replication fork structures. In a genetic assay, expression of archaeal Lhr gave a phenotype identical to the replication-coupled DNA repair enzymes Hel308 and RecQ. Purified archaeal Lhr preferentially unwound model forked DNA substrates compared with DNA duplexes, flaps and Holliday junctions, and unwound them with directionality. Single-molecule FRET measurements showed that binding of Lhr to a DNA fork causes ATP-independent distortion and base-pair melting at, or close to, the fork branchpoint. ATP-dependent directional translocation of Lhr resulted in fork DNA unwinding through the 'parental' DNA strands. Interaction of Lhr with replication forks in vivo and in vitro suggests that it contributes to DNA repair at stalled or broken DNA replication.

Original languageEnglish
Pages (from-to)2935-2947
Number of pages13
JournalBiochemical Journal
Volume477
Issue number16
DOIs
Publication statusPublished - 28 Aug 2020

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