TY - JOUR
T1 - Rif1 binds to G quadruplexes and suppresses replication over long distances
AU - Kanoh, Yutaka
AU - Matsumoto, Seiji
AU - Fukatsu, Rino
AU - Kakusho, Naoko
AU - Kono, Nobuaki
AU - Renard-Guillet, Claire
AU - Masuda, Koji
AU - Iida, Keisuke
AU - Nagasawa, Kazuo
AU - Shirahige, Katsuhiko
AU - Masai, Hisao
N1 - Funding Information:
We thank J. Horiuchi for critical reading of the manuscript and useful suggestions. We would like to thank K. Ohta and the members of his laboratory for assistance in ChIP-seq analyses, which were supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research on Priority Areas (‘non-coding DNA’). This work was supported by JSPS KAKENHI (Grant-in-Aid for Scientific Research (A) (grant nos. 23247031 and 26251004) and Grant-in-Aid for Scientific Research on Priority Areas (‘non-coding RNA’ and ‘Genome Adaptation’; grant nos. 24114520 and 25125724, respectively) to H.M. and Grant-in-Aid for Scientific Research (C) (grant no. 24570205) to S.M., Grant-in-Aid for Scientific Research (A) (grant no. 15H02369) to K.S. and Grant-in-Aid for Young Scientists (B) (grant no. 26870575) to N. Kono) and by the Naito Foundation Continuation Subsidy for Outstanding Projects (to H.M.). We thank members of our laboratory for helpful discussion.
Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/11/4
Y1 - 2015/11/4
N2 - 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.
AB - 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.
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U2 - 10.1038/nsmb.3102
DO - 10.1038/nsmb.3102
M3 - Article
C2 - 26436827
AN - SCOPUS:84948071666
SN - 1545-9993
VL - 22
SP - 889
EP - 897
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 11
ER -