Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins

Abstract
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Article and author information
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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

1. Zhang H
2. Petrie M
3. He Y
4. Peace J
5. Chiolo I
6. Aparicio O
(2019) Data from: Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins in S. cerevisiae
Dryad Digital Repository, doi:10.5061/dryad.7bm444s.

https://dx.doi.org/10.5061/dryad.7bm444s

Article and author information

Author details

Haiyang Zhang

Department of Biological Sciences, University of Southern California, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
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.
Yiwei He

Department of Biological Sciences, University of Southern California, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
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.
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.

"This ORCID iD identifies the author of this article:" 0000-0002-3080-550X
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.

"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.

Copyright

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.