Molecular Cell
Volume 30, Issue 2, 25 April 2008, Pages 156-166
Journal home page for Molecular Cell

Article
An ARS Element Inhibits DNA Replication through a SIR2-Dependent Mechanism

https://doi.org/10.1016/j.molcel.2008.02.019Get rights and content
Under an Elsevier user license
open archive

Summary

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 (IS) required SIR2 for its activity, suggesting that SIR2 inhibits origins through this sequence. Furthermore, IS elements occurred within positioned nucleosomes, and Abf1p-mediated exclusion of nucleosomes from the origin abrogated the inhibition. These data suggest that Sir2p and IS elements inhibit origin activity by promoting an unfavorable chromatin structure for pre-RC assembly.

DNA
CELLCYCLE

Cited by (0)

3

These authors contributed equally to this work.

4

Present address: Department of Oral Biology, Indiana University School of Dentistry, Indianapolis, IN 46202, USA.

5

Present address: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.