10779/crick.12620429.v1
Nausica Arnoult
Nausica
Arnoult
Adriana Correia
Adriana
Correia
Jiao Ma
Jiao
Ma
Anna Merlo
Anna
Merlo
Sara Garcia-Gomez
Sara
Garcia-Gomez
Marija Maric
Marija
Maric
Marco Tognetti
Marco
Tognetti
Christopher W Benner
Christopher W
Benner
Simon J Boulton
Simon J
Boulton
Alan Saghatelian
Alan
Saghatelian
Jan Karlseder
Jan
Karlseder
Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN
The Francis Crick Institute
2020
Cell Line
Chromatids
Chromosome Aberrations
DNA Breaks, Double-Stranded
DNA End-Joining Repair
G1 Phase
G2 Phase
Humans
Ku Autoantigen
Protein Binding
Recombinational DNA Repair
S Phase
Telomere
Boulton FC001048
General Science & Technology
2020-07-15 10:56:42
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Regulation_of_DNA_repair_pathway_choice_in_S_and_G2_phases_by_the_NHEJ_inhibitor_CYREN/12620429
Classical non-homologous end joining (cNHEJ) and homologous recombination compete for the repair of double-stranded DNA breaks during the cell cycle. Homologous recombination is inhibited during the G1 phase of the cell cycle, but both pathways are active in the S and G2 phases. However, it is unclear why cNHEJ does not always outcompete homologous recombination during the S and G2 phases. Here we show that CYREN (cell cycle regulator of NHEJ) is a cell-cycle-specific inhibitor of cNHEJ. Suppression of CYREN allows cNHEJ to occur at telomeres and intrachromosomal breaks during the S and G2 phases, and cells lacking CYREN accumulate chromosomal aberrations upon damage induction, specifically outside the G1 phase. CYREN acts by binding to the Ku70/80 heterodimer and preferentially inhibits cNHEJ at breaks with overhangs by protecting them. We therefore propose that CYREN is a direct cell-cycle-dependent inhibitor of cNHEJ that promotes error-free repair by homologous recombination during cell cycle phases when sister chromatids are present.