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An SR protein is essential for activating DNA repair in malaria parasites.
Journal of Cell Science ( IF 4 ) Pub Date : 2021-08-17 , DOI: 10.1242/jcs.258572
Manish Goyal 1 , Brajesh Kumar Singh 1 , Karina Simantov 1 , Yotam Kaufman 1 , Shiri Eshar 1 , Ron Dzikowski 1
Affiliation  

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.

中文翻译:

SR 蛋白对于激活疟疾寄生虫的 DNA 修复至关重要。

恶性疟原虫是造成人类最致命疟疾形式的寄生虫,它在宿主的红细胞内复制,在那里它遇到许多压力,导致广泛的 DNA 损伤,必须有效修复这些损伤以确保寄生虫存活。已经失去了修复 DNA 双链断裂的非同源末端连接 (NHEJ) 途径的疟疾寄生虫已经进化出独特的机制,使它们能够在如此恶劣的条件下稳健地保持基因组完整性。然而,这些适应的性质是未知的。我们展示了高度保守的 RNA 剪接因子恶性疟原虫 (Pf) SR1,在疟疾寄生虫的 DNA 修复中起着意想不到的关键作用。使用可诱导和可逆系统来操纵 PfSR1 表达,我们证明该蛋白质被招募到 DNA 损伤的病灶。虽然 PfSR1 的缺失不会损害寄生虫的生存能力,但该蛋白质对于它们从 DNA 损伤剂或暴露于青蒿素(一线抗疟药)中恢复至关重要,这表明其对 DNA 修复的必要性。这些发现为了解疟原虫 DNA 修复途径的演变以及疟原虫从抗疟治疗中恢复的能力提供了关键见解。
更新日期:2021-07-22
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