Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 2558-2566 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 27 |
| Issue number | 9 |
| Early online date | 28 May 2019 |
| DOIs | |
| Publication status | Published - 28 May 2019 |
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Keywords
- DNA Replication
- Fork Protection
- Replication stress
- Genome Integrity
- RIF1-PP1
- DNA2
- WRN
- DNA replication
- replication stress
- genome integrity
- fork protection
- RIF1
- PHOSPHORYLATION
- GENOME STABILITY
- REVERSAL
- FORK DEGRADATION
- RESTART
- END RESECTION
- STRESS
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Human RIF1-Protein Phosphatase 1 prevents degradation and breakage of nascent DNA on replication stalling. / Garzón, Javier; Ursich, Sebastian; Lopes, Massimo; Hiraga, Shin-ichiro; Donaldson, Anne D. (Corresponding Author).
In: Cell Reports, Vol. 27, No. 9, 28.05.2019, p. 2558-2566.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Human RIF1-Protein Phosphatase 1 prevents degradation and breakage of nascent DNA on replication stalling
AU - Garzón, Javier
AU - Ursich, Sebastian
AU - Lopes, Massimo
AU - Hiraga, Shin-ichiro
AU - Donaldson, Anne D.
N1 - 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.
PY - 2019/5/28
Y1 - 2019/5/28
N2 - 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.
AB - 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.
KW - DNA Replication
KW - Fork Protection
KW - Replication stress
KW - Genome Integrity
KW - RIF1-PP1
KW - DNA2
KW - WRN
KW - DNA replication
KW - replication stress
KW - genome integrity
KW - fork protection
KW - RIF1
KW - PHOSPHORYLATION
KW - GENOME STABILITY
KW - REVERSAL
KW - FORK DEGRADATION
KW - RESTART
KW - END RESECTION
KW - STRESS
UR - http://www.scopus.com/inward/record.url?scp=85065894680&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/human-rif1protein-phosphatase-1-prevents-degradation-breakage-nascent-dna-replication-stalling
U2 - 10.1016/j.celrep.2019.05.002
DO - 10.1016/j.celrep.2019.05.002
M3 - Article
C2 - 31141682
VL - 27
SP - 2558
EP - 2566
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
ER -