Abstract
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 language | English |
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Pages (from-to) | 2558-2566.e4 |
Number of pages | 14 |
Journal | Cell Reports |
Volume | 27 |
Issue number | 9 |
Early online date | 28 May 2019 |
DOIs | |
Publication status | Published - 28 May 2019 |
Keywords
- DNA Replication
- Fork Protection
- Replication stress
- Genome Integrity
- RIF1-PP1
- DNA2
- WRN
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Dive into the research topics of 'Human RIF1-Protein Phosphatase 1 Prevents Degradation and Breakage of Nascent DNA on Replication Stalling'. Together they form a unique fingerprint.Profiles
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Shinichiro Hiraga
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Senior Lecturer
- Institute of Medical Sciences
Person: Academic