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URDNA SIGNED

Origin and Protection of Unstable Repetitive DNA Elements During Sexual Reproduction

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

URDNA project word cloud

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

class principles outermost repetitive genomes myriad genome genomic intrinsically causes insights threaten breaks protection actively physiology disease rdna paradigm biology aetiology gained yeast roles anti break origin vulnerability contain experiments serve reproduction form biochemistry ribosomal first basis understand cellular instability molecular attract minimizes enzymatic fragile protects eukaryotic combination incorrect repair origins yielding isolated showed sequences vital dna stability congenital locus foresee specialized amounts array sexual crucially interrogate model boundaries human locally genomics vulnerable sites budding genetic disorders govern outlined unstable developmental caused

Project "URDNA" data sheet

The following table provides information about the project.

Coordinator	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: MUENCHEN postcode: 80539 website: n.a. 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	Germany [DE]
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-2014-STG
Funding Scheme	ERC-STG
Starting year	2015
Duration (year-month-day)	from 2015-05-01 to 2020-09-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Organization address address: HOFGARTENSTRASSE 8 city: MUENCHEN postcode: 80539 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (MUENCHEN)	coordinator	1˙500˙000.00

Map

Project objective

The objective of this proposal is to define the molecular basis behind the origin and protection of unstable repetitive DNA sequences during sexual reproduction. Eukaryotic genomes contain large amounts of repetitive elements that serve vital roles in cellular physiology. However, repetitive elements are intrinsically unstable, which is caused by a high likelihood for incorrect repair when DNA breaks form within repetitive elements. During sexual reproduction, numerous DNA breaks are actively introduced into the genome, and repetitive sequences particularly threaten genome stability during this specialized developmental program. We will use the repetitive budding yeast ribosomal (r)DNA array as a model locus to study repetitive DNA instability. Our previous work showed that the outermost elements of this large repetitive array (i.e. rDNA array boundaries) are DNA break ‘fragile sites’, which attract DNA breaks during sexual reproduction. Importantly, we isolated the first known enzymatic ‘anti-DNA break’ system, which minimizes DNA break formation at rDNA array boundaries and as such is crucially required to maintain genome stability. In the experiments outlined here, we will use a combination of genomics, molecular biology and biochemistry to: 1) Interrogate the origins of the vulnerability of the repetitive rDNA boundaries for DNA breaks, and 2) Define how a first-in-class ‘anti-DNA break’ system locally protects against DNA break formation. These studies will serve as a paradigm for repetitive DNA instability, yielding major insights into the general principles that govern protection of vulnerable genomic elements during sexual reproduction. It is well established that incorrect repair of DNA breaks involving repetitive sequences during sexual reproduction causes a myriad of human congenital disorders. Therefore, we foresee that insights gained from this work have the potential to help us understand the aetiology of human genetic disease.

Publications

List of publications.
year	authors and title	journal	last update
2015	Nadine Vincenten, Lisa-Marie Kuhl, Isabel Lam, Ashwini Oke, Alastair RW Kerr, Andreas Hochwagen, Jennifer Fung, Scott Keeney, Gerben Vader, AdÃ¨le L Marston The kinetochore prevents centromere-proximal crossover recombination during meiosis published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.10850	eLife 4	2020-03-03

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