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MitoRepairosome SIGNED

Dissecting the mechanism of DNA repair in human mitochondria

Total Cost €

0

EC-Contrib. €

0

Partnership

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 MitoRepairosome project word cloud

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

neurological    lig3    agents    exogenous    mechanism    locations    apyrimidinic    accessory    excision    anchored    repaired    mistakes    cells    attack    ber    ligase    polymerase    byproducts    compartments    oxygen    electron    instability    repairosome    complete    pol    subjected    ape1    mtdna    skeletal    cardiovascular    stored    gamma    accepted    form    inner    muscular    mechanistic    composition    spatial    aging    subunit    thein    localized    reactive    organization    leads    genetic    mitochondrial    normal    complexes    enzymes    species    constant    aptly    genomic    mammalian    bound    dna    insights    detected    defense    structures    cancer    damaging    damage    oxphos    weight    endogenous    diseases    human    membrane    base    dividing    disorders    close    exog    fundamental    proximity    oxidative    nucleus    molecular    becomes    mutations    mitochondria    lesions    components    copied    assembly    ros    readily    repair    endonuclease    phosphorylation    chain    persistence    faithfully    apurinic    transport    exo    catalytic    temporal   

Project "MitoRepairosome" data sheet

The following table provides information about the project.

Coordinator
UNIWERSYTET GDANSKI 

Organization address
address: UL. BAZYNSKIEGO 8
city: GDANSK
postcode: 80309
website: www.ug.edu.pl

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 Poland [PL]
 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-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-02-01   to  2025-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIWERSYTET GDANSKI PL (GDANSK) coordinator 1˙500˙000.00

Map

 Project objective

In mammalian cells genetic information is stored in two compartments: in the nucleus and in the mitochondria. DNA in mitochondria (mtDNA), just like in theIn mammalian cells genetic information is stored in two locations: in the nucleus and in mitochondria. DNA in mitochondria, just like in the nucleus, must be faithfully copied and mistakes (i.e. mutations due to exogenous and endogenous DNA damaging agents) lead to formation of DNA lesions. Persistence of these DNA lesions leads to genomic instability and human diseases like cardiovascular, skeletal muscular and neurological disorders, cancer as well as normal aging process. Mitochondrial DNA (mtDNA) is anchored to the inner mitochondrial membrane thus is in a close proximity to the electron transport chain and is subjected to a constant attack by reactive oxygen species (ROS), generated as byproducts of oxidative phosphorylation (OXPHOS). As a result mitochondria must have a robust DNA repair mechanism which becomes particularly important in non-dividing cells. It is accepted that DNA base excision repair (BER) pathway is a major defense mechanism against oxidative damage in human mitochondria. Aptly localized on mitochondrial inner membrane, mitochondrial BER enzymes: catalytic subunit of DNA polymerase γ (PolγA) along with its accessory subunit, DNA polymerase γ (PolγB), inner-membrane 5'-exo/endonuclease (EXOG), Apurinic/apyrimidinic endonuclease 1 (APE1) and Ligase 3 (Lig3) form a membrane-bound, high molecular weight, complexes called “mitochondrial repairosome”, capable of carrying out complete DNA repair. Although BER can be readily detected in mitochondria and major components have been identified, the spatial-temporal organization of mitochondrial repairosome and molecular mechanism by which mtDNA is repaired is not well understood. The goal of this research project is to provide fundamental mechanistic insights into the assembly, composition, activities and structures of human mitochondrial repairosome.

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