Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres", Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires, Argentina.
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
PLoS One. 2022 Dec 30;17(12):e0267329. doi: 10.1371/journal.pone.0267329. eCollection 2022.
Poly (ADP-ribose) polymerase (PARP) is responsible for the synthesis of ADP-ribose polymers, which are involved in a wide range of cellular processes such as preservation of genome integrity, DNA damage signaling and repair, molecular switches between distinct cell death pathways, and cell cycle progression. Previously, we demonstrated that the only PARP present in T. cruzi migrates to the nucleus upon genotoxic stimulus. In this work, we identify the N-terminal domain as being sufficient for TcPARP nuclear localization and describe for the first time that TcPARP is enriched in the parasite's nucleolus. We also describe that TcPARP is present in a thread-like structure that connects two dividing nuclei and co-localizes with nucleolar material and microtubules. Furthermore, ADP-ribose polymers could also be detected in this thread during mitosis. These findings represent a first approach to new potential TcPARP functions inside the nucleus and will help understand its role well beyond the largely described DNA damage response protein in trypanosomatids.
多聚(ADP-核糖)聚合酶(PARP)负责合成 ADP-核糖聚合物,这些聚合物参与广泛的细胞过程,如基因组完整性的维持、DNA 损伤信号转导和修复、不同细胞死亡途径之间的分子开关,以及细胞周期进程。此前,我们证明了在 T. cruzi 中存在的唯一 PARP 在受到遗传毒性刺激时会迁移到细胞核。在这项工作中,我们确定了 N 端结构域对于 TcPARP 核定位是足够的,并首次描述了 TcPARP 在寄生虫的核仁中富集。我们还描述了 TcPARP 存在于连接两个分裂核的线状结构中,并与核仁物质和微管共定位。此外,在有丝分裂过程中也可以在这条线上检测到 ADP-核糖聚合物。这些发现代表了在核内探索新的潜在 TcPARP 功能的首次尝试,将有助于理解其作用,而不仅仅是在原生动物中广泛描述的 DNA 损伤反应蛋白。