
The histone deacetylase Sir2 and the chromatin remodeling enzyme Fun30 regulate replication timing at the ribosomal DNA (rDNA) by controlling the positioning and activation of the Mcm replicative helicase complex.


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The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well-known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae , the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA arrays (rDNA). We have previously reported that in the absence of SIR2 , a derepressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the non-displaced MCMs. Furthermore, we found that both, activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30 . Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.

### Competing Interest Statement

The authors have declared no competing interest.

Sir2 and Fun30 regulate ribosomal DNA replication timing via Mcm helicase positioning and nucleosome occupancy

sir2-and-fun30-regulate-ribosomal-dna-replication-timing-by-modulating-mcm-helicase-positioning-and-nucleosome-occupancy


Sir2 and Fun30 Regulate Ribosomal DNA Replication Timing by Modulating Mcm Helicase Positioning and Nucleosome Occupancy
