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MitoRepairosome SIGNED

Dissecting the mechanism of DNA repair in human mitochondria

Total Cost €

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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.

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

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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