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Thesis

A role for Sum1 in HML silencing and replication initiation in Saccharomyces cerevisiae

MPS-Authors

Irlbacher,  Horst
Max Planck Society;

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Citation

Irlbacher, H. (2005). A role for Sum1 in HML silencing and replication initiation in Saccharomyces cerevisiae. PhD Thesis, Humboldt-Universität, Berlin.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-85F5-0
Abstract
The division of eukaryotic chromatin into functionally distinct domains is critical to implement gene expression programs that drive the development of multicellular organisms. Regions termed euchromatin exist in the genome that are generally conducive to transcription, whereas heterochromatin contains specialized chromatin binding proteins that repress transcription in these regions. A central question in heterochromatin biology is how the heterochromatin factors are targeted to specific genomic regions, a process that is crucial to ensure that the designated domains, and only they, are repressed in the appropriate spatial and temporal fashion. In Saccharomyces cerevisiae heterochromatinization at the silent matingtype loci HMRa and HMLα is achieved by targeting the Sir complex to these regions via a set of anchor proteins that bind to the silencers. Here, we have identified a novel heterochromatin targeting factor for HMLα, the protein Sum1, a repressor of meiotic genes during vegetative growth. Sum1 bound both in vitro and in vivo to HMLα via a functional element within the HML-E silencer, and deletion of SUM1 caused HMLα derepression. Significantly SUM1 was also required for origin activity of HML-E, suggesting a role of Sum1 in replication initiation. Our observations of a synthetic lethality between orc2-1 or orc5-1 and sum1∆ as well as a synthetic growth defect of cdc6-1, cdc7-1 and cdc45-1 with sum1 ∆ support the notion that SUM1 has a global role in replication initiation. In a genome-wide search for Sum1-regulated origins, we identified a set of autonomous replicative sequences (ARS elements) that bound both the origin recognition complex and Sum1. Full initiation activity of these origins required Sum1, and their origin activity was decreased upon removal of the Sum1 binding site. In its role as a repressor of meiosis specific genes, Sum1 often works in concert with the histone deacetylase Hst1. We found that SUM1-regulated origins also required HST1 for full activity. Taken together we propose that Sum1 is a novel replication initiation modulator for a subset of chromosomal origins.