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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.

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

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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