Origin and Protection of Unstable Repetitive DNA Elements During Sexual Reproduction

Projektinformationen

URDNA

ID Finanzhilfevereinbarung: 638197

DOI 10.3030/638197

Abgeschlossenes Projekt

EK-Unterschriftsdatum 10 April 2015

Startdatum 1 Mai 2015

Enddatum 30 September 2020

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 1 500 000,00

EU-Beitrag € 1 500 000,00

Koordiniert durch

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Ziel

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.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › genetics › DNA
• natural sciences › biological sciences › genetics › heredity
• natural sciences › biological sciences › genetics › chromosomes
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes
• natural sciences › biological sciences › genetics › genomes › eukaryotic genomes

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-StG-2014 - ERC Starting Grant

Aufforderung zur Vorschlagseinreichung

ERC-2014-STG

Finanzierungsplan

ERC-STG - Starting Grant

Gastgebende Einrichtung

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

• Netto-EU-Beitrag: € 1 500 000,00
• Adresse: HOFGARTENSTRASSE 8 ; 80539 Munchen ; Deutschland
• Region: Bayern › Oberbayern › München, Kreisfreie Stadt
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 1 500 000,00

Begünstigte (1)

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Deutschland

• Netto-EU-Beitrag: € 1 500 000,00
• Adresse: HOFGARTENSTRASSE 8 ; 80539 Munchen
• Region: Bayern › Oberbayern › München, Kreisfreie Stadt
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 1 500 000,00