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)

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)2558-2566
Number of pages13
JournalCell Reports
Volume27
Issue number9
Early online date28 May 2019
DOIs
Publication statusPublished - 28 May 2019

Fingerprint

Protein Phosphatase 1
DNA Replication
Degradation
DNA
Genomic Instability
DNA Repair
Phosphorylation
Accessories
Repair
Genes
Proteins

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 journalArticle

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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.",
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AU - Donaldson, Anne D.

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