INRS - Centre Armand-Frappier-Santé-Biotechnologie, 531 Boul. des Prairies, Laval, QC, H7V 1B7, Canada.
Department of Medicine, Université de Montréal, 2900 Blvd. Edouard Montpetit, Montreal, QC, Canada.
Apoptosis. 2021 Feb;26(1-2):9-23. doi: 10.1007/s10495-020-01649-7. Epub 2021 Jan 2.
Maintenance of genomic stability in cells is primordial for cellular integrity and protection against tumor progression. Many factors such as ultraviolet light, oxidative stress, exposure to chemical reagents, particularly mutagens and radiation, can alter the integrity of the genome. Thus, human cells are equipped with many mechanisms that prevent these irreversible lesions in the genome, as DNA repair pathways, cell cycle checkpoints, and telomeric function. These mechanisms activate cellular apoptosis to maintain DNA stability. Emerging studies have proposed a new protein in the maintenance of genomic stability: the DNA fragmentation factor (DFF). The DFF40 is an endonuclease responsible of the oligonucleosomal fragmentation of the DNA during apoptosis. The lack of DFF in renal carcinoma cells induces apoptosis without oligonucleosomal fragmentation, which poses a threat to genetic information transfer between cancerous and healthy cells. In this review, we expose the link between the DFF and genomic instability as the source of disease development.
维持细胞内基因组的稳定性对于细胞的完整性和防止肿瘤进展至关重要。许多因素，如紫外线、氧化应激、化学试剂的暴露，特别是诱变剂和辐射，都可能改变基因组的完整性。因此，人类细胞配备了许多机制来防止基因组中这些不可逆转的损伤，如 DNA 修复途径、细胞周期检查点和端粒功能。这些机制激活细胞凋亡以维持 DNA 稳定性。新的研究提出了一种维持基因组稳定性的新蛋白质：DNA 片段化因子（DFF）。DFF40 是一种内切酶，负责在细胞凋亡过程中使 DNA 寡核小体片段化。在肾癌细胞中缺乏 DFF 会诱导没有寡核小体片段化的细胞凋亡，这对癌细胞和健康细胞之间的遗传信息传递构成威胁。在这篇综述中，我们揭示了 DFF 与基因组不稳定性之间的联系，这是疾病发展的根源。
