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Nat Struct Mol Biol. 2015 Nov;22(11):889-97. doi: 10.1038/nsmb.3102. Epub 2015 Oct 5.

Rif1 binds to G quadruplexes and suppresses replication over long distances.

Author information

1
Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
2
Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
3
Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
4
Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Abstract

Rif1 regulates replication timing and repair of double-strand DNA breaks. Using a chromatin immunoprecipitation-sequencing method, we identified 35 high-affinity Rif1-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.

PMID:
26436827
DOI:
10.1038/nsmb.3102
[Indexed for MEDLINE]

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