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Molecular and structural mechanisms for metazoan replication origin specification

Total Cost €


EC-Contrib. €






 ORISPECIFICATION project word cloud

Explore the words cloud of the ORISPECIFICATION project. It provides you a very rough idea of what is the project "ORISPECIFICATION" about.

sequences    architecture    chromatin    multiple    biochemical    shaped    orc    sustain    instead    metazoan    outcomes    eukaryote    integrity    viability    structural    principles    biomedical    cell    dna    sites    domains    accurate    reaching    appears    cerevisiae    questions    instability    rely    organismal    relevance    conservative    nucleosomes    understand    depends    origins    replication    site    links    diseases    loading    prokaryotes    initiators    helicases    uncovering    implications    human    mechanistic    genomic    genetic    foremost    eukaryotes    elucidate    turn    relies    origin    determined    molecular    disorders    developmental    certain    specification    cellular    recognition    cancer    binds    underpins    ring    precisely    differentiation    auxiliary    employing    structure    semi    chromosomal    replicate    life    efforts    proteins    leads    onto    duplication    initiation    eukaryotic    termed    interaction    foundation    scientific    context    recognize    binding    specify    altered    replicative    initiator    bind   

Project "ORISPECIFICATION" data sheet

The following table provides information about the project.


Organization address
city: BASEL
postcode: 4058

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-07-01   to  2023-06-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Cellular life depends on the timely and accurate duplication of chromosomal DNA through semi-conservative replication to sustain genomic integrity and organismal viability. In all domains of life, DNA replication relies on dedicated initiator proteins that recognize and bind specific genomic sites, termed replication origins, to facilitate the loading of ring-shaped replicative helicases onto DNA. While origin recognition by initiators is determined by specific DNA sequences in prokaryotes and in the eukaryote S. cerevisiae, origin specification in higher eukaryotes instead appears to rely on chromatin context and DNA structure. Yet, how initiators help specify replication origins at the molecular level and how their binding sites are established in higher eukaryotes remain foremost and long-standing questions in the field. This research proposal focuses on uncovering the molecular and structural principles for chromosomal binding site selection by the eukaryotic initiator, the origin recognition complex (ORC), in metazoan systems. Employing integrated biochemical, structural, and cell-based approaches, we aim to 1) elucidate how ORC binds DNA and how DNA structural elements contribute to this interaction, 2) determine how nucleosomes are recognized by ORC, and 3) identify auxiliary binding partners of ORC and establish how they contribute to origin specification. The outcomes of our proposed efforts will have far-reaching implications for multiple scientific fields by defining mechanistic links between chromatin architecture and DNA replication initiation, and they will set the foundation to understand at the molecular level how the replication initiation program is altered during cell differentiation and development. Our studies also have significant biomedical relevance, as failure to precisely replicate chromosomal DNA leads to genetic instability, which in turn underpins many human diseases, including cancer and certain developmental disorders.


year authors and title journal last update
List of publications.
2019 Babatunde Ekundayo, Franziska Bleichert
Origins of DNA replication
published pages: e1008320, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1008320
PLOS Genetics 15/9 2020-04-01
2019 Franziska Bleichert
Mechanisms of replication origin licensing: a structural perspective
published pages: 195-204, ISSN: 0959-440X, DOI: 10.1016/
Current Opinion in Structural Biology 59 2020-04-01

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