RIF1 promotes replication fork protection and efficient restart to maintain genome stability

Chirantani Mukherjee, Vivek Tripathi, Eleni Maria Manolika, Anne Margriet Heijink, Giulia Ricci, Sarra Merzouk, H. Rudolf Boer, Jeroen Demmers, Marcel A. T. M. Vugt and Arnab Ray Chaudhuri ()
Additional contact information
Chirantani Mukherjee: Erasmus University Medical Center
Vivek Tripathi: Erasmus University Medical Center
Eleni Maria Manolika: Erasmus University Medical Center
Anne Margriet Heijink: University Medical Center Groningen, University of Groningen
Giulia Ricci: Erasmus University Medical Center
Sarra Merzouk: Erasmus University Medical Center
H. Rudolf Boer: University Medical Center Groningen, University of Groningen
Jeroen Demmers: Erasmus University Medical Center
Marcel A. T. M. Vugt: University Medical Center Groningen, University of Groningen
Arnab Ray Chaudhuri: Erasmus University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Homologous recombination (HR) and Fanconi Anemia (FA) pathway proteins in addition to their DNA repair functions, limit nuclease-mediated processing of stalled replication forks. However, the mechanism by which replication fork degradation results in genome instability is poorly understood. Here, we identify RIF1, a non-homologous end joining (NHEJ) factor, to be enriched at stalled replication forks. Rif1 knockout cells are proficient for recombination, but displayed degradation of reversed forks, which depends on DNA2 nuclease activity. Notably, RIF1-mediated protection of replication forks is independent of its function in NHEJ, but depends on its interaction with Protein Phosphatase 1. RIF1 deficiency delays fork restart and results in exposure of under-replicated DNA, which is the precursor of subsequent genomic instability. Our data implicate RIF1 to be an essential factor for replication fork protection, and uncover the mechanisms by which unprotected DNA replication forks can lead to genome instability in recombination-proficient conditions.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11246-1 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:10:y:2019:i:1:d:10.1038_s41467-019-11246-1

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

DOI: 10.1038/s41467-019-11246-1

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 ().