Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila

eLife

Jared T Nordman¹  Alexander Munden²  Amanda Sun²  Zhan Rong²  Simon Mallal³  Rama Gangula³ 

[1] Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, United States;Department of Biological Sciences, Vanderbilt University, Nashville, United States;Department of Medicine, Vanderbilt University School of Medicine, Nashville, United States;

关键词: DNA replication;    common fragile sites;    replication timing;    genome stability;    under replication;    polyploid;   

DOI  :  10.7554/eLife.39140

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown