An ARS element inhibits DNA replication through a SIR2-dependent mechanism.

Laboratory of Chromosome Replication, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
During G1 phase, a prereplicative complex (pre-RC) that determines where DNA synthesis initiates forms at origins. The Sir2p histone deacetylase inhibits pre-RC assembly at a subset of origins, suggesting that Sir2p inhibits DNA replication through a unique aspect of origin structure. Here, we identified five SIR2-sensitive origins on chromosomes III and VI. Linker scan analysis of two origins indicated that they share a common organization, including an inhibitory sequence positioned 3' to the sites of origin recognition complex (ORC) binding and pre-RC assembly. This inhibitory sequence (I(S)) required SIR2 for its activity, suggesting that SIR2 inhibits origins through this sequence. Furthermore, I(S) elements occurred within positioned nucleosomes, and Abf1p-mediated exclusion of nucleosomes from the origin abrogated the inhibition. These data suggest that Sir2p and I(S) elements inhibit origin activity by promoting an unfavorable chromatin structure for pre-RC assembly.
Mesh Terms:
Base Sequence, Cell Cycle Proteins, Centromere, Chromatin, Chromatin Immunoprecipitation, Chromosomes, Fungal, DNA Replication, Histone Deacetylases, Hot Temperature, Mutation, Origin Recognition Complex, Plasmids, Replication Origin, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2, Sirtuins, Suppression, Genetic
Mol. Cell Apr. 25, 2008; 30(2);156-66 [PUBMED:18439895]
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