title: Rif1 is a global regulator of timing of replication origin firing in fission yeast.
abstract: One of the long-standing questions in eukaryotic DNA replication is the mechanisms that determine where and when a particular segment of the genome is replicated. Cdc7/Hsk1 is a conserved kinase required for initiation of DNA replication and may affect the site selection and timing of origin firing. We identified rif1Δ, a null mutant of rif1(+), a conserved telomere-binding factor, as an efficient bypass mutant of fission yeast hsk1. Extensive deregulation of dormant origins over a wide range of the chromosomes occurs in rif1Δ in the presence or absence of hydroxyurea (HU). At the same time, many early-firing, efficient origins are suppressed or delayed in firing timing in rif1Δ. Rif1 binds not only to telomeres, but also to many specific locations on the arm segments that only partially overlap with the prereplicative complex assembly sites, although Rif1 tends to bind in the vicinity of the late/dormant origins activated in rif1Δ. The binding to the arm segments occurs through M to G1 phase in a manner independent of Taz1 and appears to be essential for the replication timing program during the normal cell cycle. Our data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes.
authors.affiliation: Genome Dynamics, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Hayano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanoh
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Claire
authors.initials: C
authors.lastname: Renard-Guillet
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Hisao
authors.initials: H
authors.lastname: Masai
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002503:Centromere / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D042522:DNA Replication Timing / Q000235:genetics*; D016193:G1 Phase; D017353:Gene Deletion; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018741:Replication Origin / Q000502:physiology*; D012568:Schizosaccharomyces / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C509571:Rap1 protein, S pombe; C570600:Rif1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C104344:taz1 protein, S pombe; C489406:cdc7 protein, S pombe; C094761:HSK1 protein, S pombe; D017346:Protein Serine-Threonine Kinases