Innovating Works

MitoRepairosome

Financiado
Dissecting the mechanism of DNA repair in human mitochondria
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 n... 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. ver más
31/01/2025
UG
2M€
Duración del proyecto: 63 meses Fecha Inicio: 2019-10-31
Fecha Fin: 2025-01-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2019-10-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG: ERC Starting Grant
Cerrada hace 6 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
UNIWERSYTET GDANSKI No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5