USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication

Hannah L. Mackay, Helen R. Stone, George E. Ronson, Katherine Ellis, Alexander Lanz, Yara Aghabi, Alexandra K. Walker, Katarzyna Starowicz, Alexander J. Garvin, Patrick Van Eijk, Stefan A. Koestler, Elizabeth J. Anthony, Ann Liza Piberger, Anoop S. Chauhan, Poppy Conway-Thomas, Alina Vaitsiankova, Sobana Vijayendran, James F. Beesley, Eva Petermann, Eric J. Brown, Ruth M. Densham, Simon H. Reed, Felix Dobbs, Marco Saponaro and Joanna R. Morris ()
Additional contact information
Hannah L. Mackay: University of Birmingham
Helen R. Stone: University of Birmingham
George E. Ronson: University of Birmingham
Katherine Ellis: University of Birmingham
Alexander Lanz: University of Birmingham
Yara Aghabi: University of Birmingham
Alexandra K. Walker: University of Birmingham
Katarzyna Starowicz: University of Birmingham
Alexander J. Garvin: University of Birmingham
Patrick Van Eijk: Hinxton
Stefan A. Koestler: University of Birmingham
Elizabeth J. Anthony: University of Birmingham
Ann Liza Piberger: University of Birmingham
Anoop S. Chauhan: University of Birmingham
Poppy Conway-Thomas: University of Birmingham
Alina Vaitsiankova: Falmer
Sobana Vijayendran: University of Birmingham
James F. Beesley: University of Birmingham
Eva Petermann: University of Birmingham
Eric J. Brown: University of Pennsylvania
Ruth M. Densham: University of Birmingham
Simon H. Reed: Hinxton
Felix Dobbs: Hinxton
Marco Saponaro: University of Birmingham
Joanna R. Morris: University of Birmingham

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52250-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52250-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52250-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().