Ryan Buckley
Mechanistic insights into Lhr helicase function in DNA repair
Buckley, Ryan; Kramm, Kevin; Cooper, Christopher D. O.; Grohmann, Dina; Bolt, Edward L
Authors
Kevin Kramm
Christopher D. O. Cooper
Dina Grohmann
ED BOLT ED.BOLT@NOTTINGHAM.AC.UK
Associate Professor
Abstract
The DNA helicase 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 to 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.
Citation
Buckley, R., Kramm, K., Cooper, C. D. O., Grohmann, D., & Bolt, E. L. (2020). Mechanistic insights into Lhr helicase function in DNA repair. Biochemical Journal, 477(16), 2935–2947. https://doi.org/10.1042/bcj20200379
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 23, 2020 |
Online Publication Date | Aug 19, 2020 |
Publication Date | Aug 19, 2020 |
Deposit Date | Jul 29, 2020 |
Publicly Available Date | Aug 20, 2021 |
Journal | Biochemical Journal |
Print ISSN | 0264-6021 |
Electronic ISSN | 1470-8728 |
Publisher | Portland Press |
Peer Reviewed | Peer Reviewed |
Volume | 477 |
Issue | 16 |
Pages | 2935–2947 |
DOI | https://doi.org/10.1042/bcj20200379 |
Keywords | Cell Biology; Biochemistry; Molecular Biology |
Public URL | https://nottingham-repository.worktribe.com/output/4795518 |
Publisher URL | https://portlandpress.com/biochemj/article/477/16/2935/225885/Mechanistic-insights-into-Lhr-helicase-function-in |
Files
Mechanistic insights into Lhr helicase function in DNA repair
(3.3 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
You might also like
Adaptation processes that build CRISPR immunity: creative destruction, updated
(2019)
Journal Article
CRISPR-Cas immunity, DNA repair and genome stability
(2018)
Journal Article
Cas3 Protein—A Review of a Multi-Tasking Machine
(2020)
Journal Article