Exonuclease action of replicative polymerase gamma drives damage-induced mitochondrial DNA clearance DOI Creative Commons
Akshaya Seshadri, Anjana Badrinarayanan

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 29, 2024

Abstract Mitochondrial DNA (mtDNA) replication is essential for mitochondrial function. This carried out by a dedicated polymerase gamma, with 5’-3’ and 3’-5’ proofreading/ exonuclease activity. Perturbations to either properties can have pathological consequences. Predominant sources stress are lesions, such as those induced oxidative damage. How mtDNA lesions affect the activity stability in vivo not fully understood. To address this, we induce mtDNA-specific damage S. cerevisiae. We observe that results significant loss. loss occurs independent of cell cycle progression or division, suggesting an active mechanism damaged clearance. implicate this clearance, rates being affected cellular dNTP levels. propose model where encounter transitions its from synthesis degradation, resulting Overall, our findings reveal context-dependent, selective regulation two critical but opposing functions gamma ensure genome integrity.

Язык: Английский

Exonuclease action of replicative polymerase gamma drives damage-induced mitochondrial DNA clearance DOI Creative Commons
Akshaya Seshadri, Anjana Badrinarayanan

EMBO Reports, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Язык: Английский

Процитировано

0

Exonuclease action of replicative polymerase gamma drives damage-induced mitochondrial DNA clearance DOI Creative Commons
Akshaya Seshadri, Anjana Badrinarayanan

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 29, 2024

Abstract Mitochondrial DNA (mtDNA) replication is essential for mitochondrial function. This carried out by a dedicated polymerase gamma, with 5’-3’ and 3’-5’ proofreading/ exonuclease activity. Perturbations to either properties can have pathological consequences. Predominant sources stress are lesions, such as those induced oxidative damage. How mtDNA lesions affect the activity stability in vivo not fully understood. To address this, we induce mtDNA-specific damage S. cerevisiae. We observe that results significant loss. loss occurs independent of cell cycle progression or division, suggesting an active mechanism damaged clearance. implicate this clearance, rates being affected cellular dNTP levels. propose model where encounter transitions its from synthesis degradation, resulting Overall, our findings reveal context-dependent, selective regulation two critical but opposing functions gamma ensure genome integrity.

Язык: Английский

Процитировано

0