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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.

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

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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