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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.

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

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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