Jia Pan-Pan, Junaid Muhammad, Ma Yan-Bo, Ahmad Farooq, Jia Yong-Fang, Li Wei-Guo, Pei De-Sheng
Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 401122, China; College of Life Science, Henan Normal University, Xinxiang 453007, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 401122, China; University of Chinese Academy of Sciences, Beijing 100049, China.
DNA Repair (Amst). 2017 Nov;59:9-19. doi: 10.1016/j.dnarep.2017.09.001. Epub 2017 Sep 6.
DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. In the maturation of Okazaki fragments, DNA2 acts synergistically with other enzymes to cleave the DNA-RNA primer flaps via different pathways. DNA2 is also involved in the stability of mitochondrial DNA and the maintenance of telomeres. Moreover, DNA2 potentially participates in controlling the cell cycle by repairing the DNA replication faults at main checkpoints. In addition, previous evidences demonstrated that DNA2 also functions in the repair process of DNA damages, such as base excision repair (BER). Currently, large studies revealed the structures and functions of DNA2 in prokaryotes and unicellular eukaryotes, such as bacteria and yeast. However, the studies that highlighted the functions of human DNA2 (hDNA2) and the relationships with other multifunctional proteins are still elusive, and more precise investigations are immensely needed. Therefore, this review mainly encompasses the key functions of DNA2 in human cells with various aspects, especially focusing on the genome integrity, and also generalizes the recent insights to the mechanisms related to the occurrence of cancer and other diseases potentially linked to the mutations in DNA2.
DNA核酸酶/解旋酶2（DNA2）是一种保护基因组传递高保真度的多功能蛋白质，在DNA复制和修复过程中发挥关键作用。在冈崎片段成熟过程中，DNA2与其他酶协同作用，通过不同途径切割DNA-RNA引物瓣。DNA2还参与线粒体DNA的稳定性和端粒的维持。此外，DNA2可能通过修复主要检查点处的DNA复制错误来参与细胞周期的调控。此外，先前的证据表明，DNA2在DNA损伤的修复过程中也发挥作用，如碱基切除修复（BER）。目前，大量研究揭示了DNA2在原核生物和单细胞真核生物（如细菌和酵母）中的结构和功能。然而，突出人类DNA2（hDNA2）功能及其与其他多功能蛋白质关系的研究仍然难以捉摸，因此迫切需要更精确的研究。因此，本综述主要从多个方面阐述了DNA2在人类细胞中的关键功能，尤其关注基因组完整性，同时总结了近期关于DNA2突变可能与癌症及其他疾病发生相关机制的见解。
