Acute Smc5/6 depletion reveals its primary role in rDNA replication by restraining recombination at fork pausing sites Journal Article


Authors: Peng, X. P.; Lim, S.; Li, S.; Marjavaara, L.; Chabes, A.; Zhao, X.
Article Title: Acute Smc5/6 depletion reveals its primary role in rDNA replication by restraining recombination at fork pausing sites
Abstract: Smc5/6, a member of the conserved SMC family of complexes, is essential for growth in most organisms. Its exact functions in a mitotic cell cycle are controversial, as chronic Smc5/6 loss-of-function alleles produce varying phenotypes. To circumvent this issue, we acutely depleted Smc5/6 in budding yeast and determined the first cell cycle consequences of Smc5/6 removal. We found a striking primary defect in replication of the ribosomal DNA (rDNA) array. Each rDNA repeat contains a programmed replication fork barrier (RFB) established by the Fob1 protein. Fob1 removal improves rDNA replication in Smc5/6 depleted cells, implicating Smc5/6 in the management of programmed fork pausing. A similar improvement is achieved by removing the DNA helicase Mph1 whose recombinogenic activity can be inhibited by Smc5/6 under DNA damage conditions. DNA 2D gel analyses further show that Smc5/6 loss increases recombination structures at RFB regions; moreover, mph1∆ and fob1∆ similarly reduce this accumulation. These findings point to an important mitotic role for Smc5/6 in restraining recombination events when protein barriers in rDNA stall replication forks. As rDNA maintenance influences multiple essential cellular processes, Smc5/6 likely links rDNA stability to overall mitotic growth. © 2018 Peng et al.
Journal Title: PLoS Genetics
Volume: 14
Issue: 1
ISSN: 1553-7390
Publisher: Public Library of Science  
Date Published: 2018-01-23
Start Page: e1007129
Language: English
DOI: 10.1371/journal.pgen.1007129
PROVIDER: scopus
PMCID: PMC5779651
PUBMED: 29360860
DOI/URL:
Notes: Article -- Export Date: 1 March 2018 -- Source: Scopus
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MSK Authors
  1. Xiaolan Zhao
    55 Zhao
  2. Xiao Peng
    4 Peng
  3. Shelly Lim
    1 Lim
  4. Shibai Li
    1 Li