Human RIF1-Protein Phosphatase 1 Prevents Degradation and Breakage of Nascent DNA on Replication Stalling

Javier Garzón, Sebastian Ursich, Massimo Lopes, Shin-ichiro Hiraga, Anne D. Donaldson* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)
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RIF1 is a multifunctional protein implicated in controlling DNA replication and repair. Here we show that human RIF1 protects nascent DNA from over-degradation at stalled replication forks. The major nuclease resecting nascent DNA in the absence of RIF1 is DNA2, operating with WRN as an accessory helicase. We show that RIF1 acts with Protein Phosphatase 1 to prevent over-degradation, and that RIF1 limits phosphorylation of WRN at sites implicated in resection control. Protection by RIF1 against inappropriate degradation prevents accumulation of DNA breakage. Our observations uncover a crucial function of human RIF1 in preventing genome instability by protecting forks from unscheduled DNA2-WRN-mediated degradation.
Original languageEnglish
Pages (from-to)2558-2566.e4
Number of pages14
JournalCell Reports
Issue number9
Early online date28 May 2019
Publication statusPublished - 28 May 2019

Bibliographical note

We thank the Microscopy Core and Proteomics Core Facilities at Aberdeen University for assistance and analysis. pCMV-Flag-WRN plasmid was kindly gifted by Pietro Pichierri. NSC-105808 from Grzegorz Ira lab was gifted by Alessandro Vindigni. We thank all the members of our lab and Takashi Kubota for helpful discussions. This research was supported by Cancer Research UK Programme Award A19059 to ADD and SH.


  • DNA Replication
  • Fork Protection
  • Replication stress
  • Genome Integrity
  • RIF1-PP1
  • DNA2
  • WRN


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