1. Chromosomes and Gene Expression
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Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins

  1. Haiyang Zhang
  2. Meghan V Petrie
  3. Yiwei He
  4. Jared M Peace
  5. Irene E Chiolo
  6. Oscar M Aparicio  Is a corresponding author
  1. University of Southern California, United States
Research Article
  • Cited 11
  • Views 1,059
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Cite this article as: eLife 2019;8:e45512 doi: 10.7554/eLife.45512

Abstract

Chromosomal DNA elements are organized into spatial domains within the eukaryotic nucleus. Sites undergoing DNA replication, high-level transcription, and repair of double-strand breaks coalesce into foci, although the significance and mechanisms giving rise to these dynamic structures are poorly understood. In S. cerevisiae, replication origins occupy characteristic subnuclear localizations that anticipate their initiation timing during S phase. Here, we link localization of replication origins in G1 phase with Fkh1 activity, which is required for their early replication timing. Using a Fkh1-dependent origin relocalization assay, we determine that execution of Dbf4-dependent kinase function, including Cdc45 loading, results in dynamic relocalization of a replication origin from the nuclear periphery to the interior in G1 phase. Origin mobility increases substantially with Fkh1-driven relocalization. These findings provide novel molecular insight into the mechanisms that govern dynamics and spatial organization of DNA replication origins and possibly other functional DNA elements.

Data availability

Imaging quantification, statistical analysis, sequencing data and MatLab scripts have been deposited in Dryad.

The following data sets were generated

Article and author information

Author details

  1. Haiyang Zhang

    Department of Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Meghan V Petrie

    Department of Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yiwei He

    Department of Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jared M Peace

    Department of Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Irene E Chiolo

    Department of Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3080-550X
  6. Oscar M Aparicio

    Department of Biological Sciences, University of Southern California, Los Angeles, United States
    For correspondence
    oaparici@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5591-0277

Funding

National Institute of General Medical Sciences (R01-GMS 05494)

  • Oscar M Aparicio

National Institute of General Medical Sciences (R01-GMS 117376)

  • Irene E Chiolo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bruce Stillman, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: January 25, 2019
  2. Accepted: May 13, 2019
  3. Accepted Manuscript published: May 14, 2019 (version 1)
  4. Version of Record published: May 23, 2019 (version 2)

Copyright

© 2019, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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