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1: Mol Cell. 2008 Apr 25;30(2):156-66.
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An ARS element inhibits DNA replication through a SIR2-dependent mechanism.

Crampton A, Chang F, Pappas DL Jr, Frisch RL, Weinreich M.

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.

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PMID: 18439895 [PubMed - indexed for MEDLINE]