Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 22, Issue 11, Pages 889-897Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3102
Keywords
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Funding
- Japan Society for the Promotion of Science (JSPS)
- JSPS KAKENHI [23247031, 26251004, 24114520, 25125724, 24570205, 15H02369, 26870575]
- Naito Foundation
- Grants-in-Aid for Scientific Research [26870575, 26560444, 24114520, 15H02369, 24570205, 26282214] Funding Source: KAKEN
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Rif1 regulates replication timing and repair of double-strand DNA breaks. Using a chromatin immunoprecipitation-sequencing method, we identified 35 high-affinity kill-binding sites in fission yeast chromosomes. Binding sites tended to be located near dormant origins and to contain at least two copies of a conserved motif, CNWWGTGGGGG. Base substitution within these motifs resulted in complete loss of Rif1 binding and in activation of late-firing or dormant origins located up to 50 kb away. We show that Rif1-binding sites adopt G quadruplex-like structures in vitro, in a manner dependent on the conserved sequence and on other G tracts, and that purified Rif1 preferentially binds to this structure. These results suggest that Rif1 recognizes and binds G quadruplex-like structures at selected intergenic regions, thus generating local chromatin structures that may exert long-range suppressive effects on origin firing.
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