Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila
Control of DNA copy number is essential to maintain genome stability and ensure proper cell and tissue function. In Drosophila polyploid cells, the SNF2-domain-containing SUUR protein inhibits replication fork progression within specific regions of the genome to promote DNA underreplication. While dissecting the function of SUUR's SNF2 domain, we identified an interaction between SUUR and Rif1. Rif1 has many roles in DNA metabolism and regulates the replication timing program. We demonstrate that repression of DNA replication is dependent on Rif1. Rif1 localizes to active replication forks in a partially SUUR-dependent manner and directly regulates replication fork progression. Importantly, SUUR associates with replication forks in the absence of Rif1, indicating that Rif1 acts downstream of SUUR to inhibit fork progression. Our findings uncover an unrecognized function of the Rif1 protein as a regulator of replication fork progression.
Sequencing data have been deposited in GEO under accession code GSE114370
Rif1 inhibits replication fork progression and controls copy number in Drosophila.Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE114370).
Article and author information
National Institutes of Health (5R00GM104151)
- Jared T Nordman
National Institutes of Health (P30 AI110527)
- Simon Mallal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Michael R Botchan, University of California, Berkeley, United States
- Received: June 12, 2018
- Accepted: October 1, 2018
- Accepted Manuscript published: October 2, 2018 (version 1)
- Version of Record published: October 12, 2018 (version 2)
© 2018, Munden 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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