DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells

Szymon A. Barwacz, Katrine Lundgaard, Wei Wu, Philipp H. Richter, Liqun Ren, Rahul Bhowmick, Marisa M. Gonçalves Dinis, Masato T. Kanemaki and Ying Liu ()
Additional contact information
Szymon A. Barwacz: University of Copenhagen
Katrine Lundgaard: University of Copenhagen
Wei Wu: University of Copenhagen
Philipp H. Richter: University of Copenhagen
Liqun Ren: University of Copenhagen
Rahul Bhowmick: University of Copenhagen
Marisa M. Gonçalves Dinis: University of Copenhagen
Masato T. Kanemaki: National Institute of Genetics, Research Organization of Information and Systems (ROIS); Graduate Institute for Advanced Studies, SOKENDAI
Ying Liu: University of Copenhagen

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Mitotic DNA synthesis (MiDAS) serves to complete the replication of genomic loci that are not fully replicated in S phase in response to replication stress. Previous studies suggest that MiDAS might proceed via break-induced DNA replication, a sub-pathway of homologous recombination repair activated at broken or collapsed replication forks. We set out to define whether DNA double strand break end-resection factors play a role in MiDAS. Here, we show that several core end-resection factors, including MRE11, CtIP and BRCA1 are essential for MiDAS. In addition, while loss of WRN or DNA2 impairs MiDAS, there is no requirement for other known end-resection factors such as EXO1 and BLM. Moreover, both the exonuclease and the helicase activities of WRN contribute to MiDAS. Because oncogene-induced replication stress is common in cancers, targeting of WRN or other factors required for MiDAS could facilitate the development of targeted cancer therapies.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63292-7 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:16:y:2025:i:1:d:10.1038_s41467-025-63292-7

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

DOI: 10.1038/s41467-025-63292-7

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 ().