title: Initiation of DNA replication from non-canonical sites on an origin-depleted chromosome.
abstract: Eukaryotic DNA replication initiates from multiple sites on each chromosome called replication origins (origins). In the budding yeast Saccharomyces cerevisiae, origins are defined at discrete sites. Regular spacing and diverse firing characteristics of origins are thought to be required for efficient completion of replication, especially in the presence of replication stress. However, a S. cerevisiae chromosome III harboring multiple origin deletions has been reported to replicate relatively normally, and yet how an origin-deficient chromosome could accomplish successful replication remains unknown. To address this issue, we deleted seven well-characterized origins from chromosome VI, and found that these deletions do not cause gross growth defects even in the presence of replication inhibitors. We demonstrated that the origin deletions do cause a strong decrease in the binding of the origin recognition complex. Unexpectedly, replication profiling of this chromosome showed that DNA replication initiates from non-canonical loci around deleted origins in yeast. These results suggest that replication initiation can be unexpectedly flexible in this organism.
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Molecular and Cellular Biology Program, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Naomi L
authors.initials: NL
authors.lastname: Bogenschutz
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Jairo
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tsukiyama
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics*; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D051738:Origin Recognition Complex / Q000235:genetics*; D018741:Replication Origin / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*
chemical_list: D004271:DNA, Fungal; D051738:Origin Recognition Complex