A link between ORC-origin binding mechanisms and origin activation time revealed in budding yeast

Hoggard, Timothy, Shor, Erika, Müller, Carolin A., Nieduszynski, Conrad A. ORCID: https://orcid.org/0000-0003-2001-076X and Fox, Catherine A. (2013) A link between ORC-origin binding mechanisms and origin activation time revealed in budding yeast. PLoS Genetics, 9 (9). ISSN 1553-7390

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Abstract

Eukaryotic DNA replication origins are selected in G1-phase when the origin recognition complex (ORC) binds chromosomal positions and triggers molecular events culminating in the initiation of DNA replication (a.k.a. origin firing) during S-phase. Each chromosome uses multiple origins for its duplication, and each origin fires at a characteristic time during S-phase, creating a cell-type specific genome replication pattern relevant to differentiation and genome stability. It is unclear whether ORC-origin interactions are relevant to origin activation time. We applied a novel genome-wide strategy to classify origins in the model eukaryote Saccharomyces cerevisiae based on the types of molecular interactions used for ORC-origin binding. Specifically, origins were classified as DNA-dependent when the strength of ORC-origin binding in vivo could be explained by the affinity of ORC for origin DNA in vitro, and, conversely, as 'chromatin-dependent' when the ORC-DNA interaction in vitro was insufficient to explain the strength of ORC-origin binding in vivo. These two origin classes differed in terms of nucleosome architecture and dependence on origin-flanking sequences in plasmid replication assays, consistent with local features of chromatin promoting ORC binding at 'chromatin-dependent' origins. Finally, the 'chromatin-dependent' class was enriched for origins that fire early in S-phase, while the DNA-dependent class was enriched for later firing origins. Conversely, the latest firing origins showed a positive association with the ORC-origin DNA paradigm for normal levels of ORC binding, whereas the earliest firing origins did not. These data reveal a novel association between ORC-origin binding mechanisms and the regulation of origin activation time.

Item Type:	Article
Uncontrolled Keywords:	ecology, evolution, behavior and systematics,molecular biology,genetics,genetics(clinical),cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1100/1105
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	08 Sep 2022 07:31
Last Modified:	04 Jul 2023 10:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/87881
DOI:	10.1371/journal.pgen.1003798

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