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A role for a replicator dominance mechanism in silencing

Authors :
Madeleine A. Palacios DeBeer
Catherine A. Fox
Source :
The EMBO Journal. 18:3808-3819
Publication Year :
1999
Publisher :
Wiley, 1999.

Abstract

The role of the natural HMR-E silencer in modulating replication initiation and silencing by the origin recognition complex (ORC) was examined. When natural HMR-E was the only silencer controlling HMR, the silencer's ORC-binding site (ACS) was dispensable for replication initiation but essential for silencing, indicating that a non-silencer chromosomal replicator(s) existed in close proximity to the silencer. Further analysis revealed that regions flanking both sides of HMR-E contained replicators. In contrast to replication initiation by the intact silencer, initiation by the non-silencer replicator(s) was abolished in an orc2-1 mutant, indicating that these replicators were extremely sensitive to defects in ORC. Remarkably, the activity of one of the non-silencer replicators correlated with reduced silencing; inactivation of these replicators caused by either the orc2-1 mutation or the deletion of flanking sequences enhanced silencing. These data were consistent with a role for the ORC bound to the HMR-E silencer ACS in suppressing the function of neighboring ORC molecules capable of inhibiting silencing, and indicated that differences in ORC-binding sites within HMR itself had profound effects on ORC function. Moreover, replication initiation by natural HMR-E was inefficient, suggesting that closely spaced replicators within HMR contributed to an inhibition of replication initiation.

Details

ISSN :
14602075
Volume :
18
Database :
OpenAIRE
Journal :
The EMBO Journal
Accession number :
edsair.doi.dedup.....d5a159ca37d78a55ee3527e2c1192521
Full Text :
https://doi.org/10.1093/emboj/18.13.3808