title: Mrc1 marks early-firing origins and coordinates timing and efficiency of initiation in fission yeast.
abstract: How early- and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing origins in a manner independent of Cdc45 and Hsk1 kinase in the fission yeast Schizosaccharomyces pombe. In mrc1Δ cells (and in swi1Δ cells to some extent), efficiency of firing is stimulated, and its timing is advanced selectively at those origins that are normally bound by Mrc1. In contrast, the late or inefficient origins which are not bound by Mrc1 are not activated in mrc1Δ cells. The enhanced firing and precocious Cdc45 loading at Mrc1-bound early-firing origins are not observed in a checkpoint mutant of mrc1, suggesting that non-checkpoint function is involved in maintaining the normal program of early-firing origins. We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein.
authors.affiliation: Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, 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: Hisao
authors.initials: H
authors.lastname: Masai
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D015825:Chromosomes, Fungal; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D064148:Minichromosome Maintenance Complex Component 4; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D018741:Replication Origin / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: C116395:CDC45 protein, S pombe; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C533276:MRC1 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C513096:swi1 protein, S pombe; D064148:Minichromosome Maintenance Complex Component 4; C078490:mcm4 protein, S pombe