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 d...
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doaj-a87f4d63fb7f45cf9f60ab32581ca0e82021-05-05T16:11:07ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.39140Rif1 inhibits replication fork progression and controls DNA copy number in DrosophilaAlexander Munden0Zhan Rong1Amanda Sun2Rama Gangula3Simon Mallal4Jared T Nordman5https://orcid.org/0000-0002-6612-3201Department of Biological Sciences, Vanderbilt University, Nashville, United StatesDepartment of Biological Sciences, Vanderbilt University, Nashville, United StatesDepartment of Biological Sciences, Vanderbilt University, Nashville, United StatesDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, United States; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, United StatesDepartment of Biological Sciences, Vanderbilt University, Nashville, United StatesControl 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.https://elifesciences.org/articles/39140DNA replicationcommon fragile sitesreplication timinggenome stabilityunder replicationpolyploid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexander Munden Zhan Rong Amanda Sun Rama Gangula Simon Mallal Jared T Nordman |
spellingShingle |
Alexander Munden Zhan Rong Amanda Sun Rama Gangula Simon Mallal Jared T Nordman Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila eLife DNA replication common fragile sites replication timing genome stability under replication polyploid |
author_facet |
Alexander Munden Zhan Rong Amanda Sun Rama Gangula Simon Mallal Jared T Nordman |
author_sort |
Alexander Munden |
title |
Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila |
title_short |
Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila |
title_full |
Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila |
title_fullStr |
Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila |
title_full_unstemmed |
Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila |
title_sort |
rif1 inhibits replication fork progression and controls dna copy number in drosophila |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-10-01 |
description |
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. |
topic |
DNA replication common fragile sites replication timing genome stability under replication polyploid |
url |
https://elifesciences.org/articles/39140 |
work_keys_str_mv |
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1721459582168989696 |