The human RIF1-Long isoform interacts with BRCA1 to promote recombinational fork repair under DNA replication stress

Qianqian Dong, Matthew Day, Yuichiro Saito, Emma Parker, Lotte P. Watts, Masato T. Kanemaki, Antony W. Oliver, Laurence H. Pearl, Shin-ichiro Hiraga () and Anne D. Donaldson ()
Additional contact information
Qianqian Dong: University of Aberdeen
Matthew Day: University of Sussex
Yuichiro Saito: Research Organization of Information and Systems (ROIS)
Emma Parker: University of Aberdeen
Lotte P. Watts: University of Aberdeen
Masato T. Kanemaki: Research Organization of Information and Systems (ROIS)
Antony W. Oliver: University of Sussex
Laurence H. Pearl: University of Sussex
Shin-ichiro Hiraga: University of Aberdeen
Anne D. Donaldson: University of Aberdeen

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract RIF1 is a multifunctional protein that regulates DNA replication and repair. RIF1-deficient cells are hypersensitive to DNA replication stress. Of the two alternatively spliced RIF1 isoforms, called RIF1-Short and RIF1-Long, the RIF1-Long isoform is more capable than RIF1-Short in supporting cell recovery from replication stress. Examining replication stress resistance mechanisms specific to RIF1-Long, we find that prolonged replication stress unexpectedly induces interaction of RIF1-Long with BRCA1. Mechanistically, a phosphorylated SPKF motif unique to the RIF1-Long isoform binds the tandem BRCT domain of BRCA1. BRCA1–RIF1-Long interaction is strongly down-regulated through dephosphorylation by RIF1-associated Protein Phosphatase 1. BRCA1–RIF1-Long interaction requires ATR signaling, and occurs predominantly during S phase. Loss of RIF1-Long impairs the formation of RAD51 foci, and reduces the efficiency of homology-mediated repair at broken replication forks. In summary, our investigation establishes RIF1-Long as a new functional binding partner of the BRCA1-BRCT domain, crucial to protect cells from extended DNA replication stress by enabling RAD51-dependent repair of broken replication forks.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60817-y 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_s41467-025-60817-y

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

DOI: 10.1038/s41467-025-60817-y

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 ().