An SR protein is essential for activating DNA repair in malaria parasites.
J Cell Sci
; 134(16)2021 08 15.
Article
em En
| MEDLINE
| ID: mdl-34291805
ABSTRACT
Plasmodium falciparum, the parasite responsible for the deadliest form of human malaria, replicates within the erythrocytes of its host, where it encounters numerous pressures that cause extensive DNA damage, which must be repaired efficiently to ensure parasite survival. Malaria parasites, which have lost the non-homologous end joining (NHEJ) pathway for repairing DNA double-strand breaks, have evolved unique mechanisms that enable them to robustly maintain genome integrity under such harsh conditions. However, the nature of these adaptations is unknown. We show that a highly conserved RNA splicing factor, P. falciparum (Pf)SR1, plays an unexpected and crucial role in DNA repair in malaria parasites. Using an inducible and reversible system to manipulate PfSR1 expression, we demonstrate that this protein is recruited to foci of DNA damage. Although loss of PfSR1 does not impair parasite viability, the protein is essential for their recovery from DNA-damaging agents or exposure to artemisinin, the first-line antimalarial drug, demonstrating its necessity for DNA repair. These findings provide key insights into the evolution of DNA repair pathways in malaria parasites as well as the ability of the parasite to recover from antimalarial treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Parasitos
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Malária Falciparum
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Malária
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Israel