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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