The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication

Erika Shor, Christopher L. Warren, Joshua Tietjen, Zhonggang Hou, Ulrika Müller, Ilaria Alborelli, Florence H. Gohard, Adrian I. Yemm, Lev Borisov, James Broach, Michael Weinreich, Conrad A. Nieduszynski, Aseem Z. Ansari, Catherine A. Fox

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The origin recognition complex (ORC) marks chromosomal sites as replication origins and is essential for replication initiation. In yeast, ORC also binds to DNA elements called silencers, where its primary function is to recruit silent information regulator (SIR) proteins to establish transcriptional silencing. Indeed, silencers function poorly as chromosomal origins. Several genetic, molecular, and biochemical studies of HMR-E have led to a model proposing that when ORC becomes limiting in the cell (such as in the orc2-1 mutant) only sites that bind ORC tightly (such as HMR-E) remain fully occupied by ORC, while lower affinity sites, including many origins, lose ORC occupancy. Since HMR-E possessed a unique non-replication function, we reasoned that other tight sites might reveal novel functions for ORC on chromosomes. Therefore, we comprehensively determined ORC "affinity" genome-wide by performing an ORC ChIP-on-chip in ORC2 and orc2-1 strains. Here we describe a novel group of orc2-1-resistant ORC-interacting chromosomal sites (ORF-ORC sites) that did not function as replication origins or silencers. Instead, ORF-ORC sites were comprised of protein-coding regions of highly transcribed metabolic genes. In contrast to the ORC-silencer paradigm, transcriptional activation promoted ORC association with these genes. Remarkably, ORF-ORC genes were enriched in proximity to origins of replication and, in several instances, were transcriptionally regulated by these origins. Taken together, these results suggest a surprising connection among ORC, replication origins, and cellular metabolism.

Original languageEnglish (US)
Article numbere1000755
JournalPLoS Genetics
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2009

Fingerprint

Origin Recognition Complex
replication origin
Replication Origin
open reading frames
gene
molecular genetics
Genes
genes
transcriptional activation
Open Reading Frames
yeasts
chromosomes
mutants
metabolism
genome
DNA
Molecular Biology
proteins
Transcriptional Silencer Elements
cells

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Shor, E., Warren, C. L., Tietjen, J., Hou, Z., Müller, U., Alborelli, I., ... Fox, C. A. (2009). The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication. PLoS Genetics, 5(12), [e1000755]. https://doi.org/10.1371/journal.pgen.1000755
Shor, Erika ; Warren, Christopher L. ; Tietjen, Joshua ; Hou, Zhonggang ; Müller, Ulrika ; Alborelli, Ilaria ; Gohard, Florence H. ; Yemm, Adrian I. ; Borisov, Lev ; Broach, James ; Weinreich, Michael ; Nieduszynski, Conrad A. ; Ansari, Aseem Z. ; Fox, Catherine A. / The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication. In: PLoS Genetics. 2009 ; Vol. 5, No. 12.
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Shor, E, Warren, CL, Tietjen, J, Hou, Z, Müller, U, Alborelli, I, Gohard, FH, Yemm, AI, Borisov, L, Broach, J, Weinreich, M, Nieduszynski, CA, Ansari, AZ & Fox, CA 2009, 'The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication', PLoS Genetics, vol. 5, no. 12, e1000755. https://doi.org/10.1371/journal.pgen.1000755

The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication. / Shor, Erika; Warren, Christopher L.; Tietjen, Joshua; Hou, Zhonggang; Müller, Ulrika; Alborelli, Ilaria; Gohard, Florence H.; Yemm, Adrian I.; Borisov, Lev; Broach, James; Weinreich, Michael; Nieduszynski, Conrad A.; Ansari, Aseem Z.; Fox, Catherine A.

In: PLoS Genetics, Vol. 5, No. 12, e1000755, 01.12.2009.

Research output: Contribution to journalArticle

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T1 - The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication

AU - Shor, Erika

AU - Warren, Christopher L.

AU - Tietjen, Joshua

AU - Hou, Zhonggang

AU - Müller, Ulrika

AU - Alborelli, Ilaria

AU - Gohard, Florence H.

AU - Yemm, Adrian I.

AU - Borisov, Lev

AU - Broach, James

AU - Weinreich, Michael

AU - Nieduszynski, Conrad A.

AU - Ansari, Aseem Z.

AU - Fox, Catherine A.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - The origin recognition complex (ORC) marks chromosomal sites as replication origins and is essential for replication initiation. In yeast, ORC also binds to DNA elements called silencers, where its primary function is to recruit silent information regulator (SIR) proteins to establish transcriptional silencing. Indeed, silencers function poorly as chromosomal origins. Several genetic, molecular, and biochemical studies of HMR-E have led to a model proposing that when ORC becomes limiting in the cell (such as in the orc2-1 mutant) only sites that bind ORC tightly (such as HMR-E) remain fully occupied by ORC, while lower affinity sites, including many origins, lose ORC occupancy. Since HMR-E possessed a unique non-replication function, we reasoned that other tight sites might reveal novel functions for ORC on chromosomes. Therefore, we comprehensively determined ORC "affinity" genome-wide by performing an ORC ChIP-on-chip in ORC2 and orc2-1 strains. Here we describe a novel group of orc2-1-resistant ORC-interacting chromosomal sites (ORF-ORC sites) that did not function as replication origins or silencers. Instead, ORF-ORC sites were comprised of protein-coding regions of highly transcribed metabolic genes. In contrast to the ORC-silencer paradigm, transcriptional activation promoted ORC association with these genes. Remarkably, ORF-ORC genes were enriched in proximity to origins of replication and, in several instances, were transcriptionally regulated by these origins. Taken together, these results suggest a surprising connection among ORC, replication origins, and cellular metabolism.

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