Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.
Environ Mol Mutagen. 2012 Dec;53(9):645-65. doi: 10.1002/em.21731. Epub 2012 Sep 22.
In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this contribution, which included the isolation and characterization of Escherichia coli DNA polymerase I. Now there are 15 known DNA polymerases in mammalian cells that belong to four different families. These DNA polymerases function in many different cellular processes including DNA replication, DNA repair, and damage tolerance. Several biochemical and cell biological studies have provoked a further investigation of DNA polymerase function using mouse models in which polymerase genes have been altered using gene-targeting techniques. The phenotypes of mice harboring mutant alleles reveal the prominent role of DNA polymerases in embryogenesis, prevention of premature aging, and cancer suppression.
1956 年,亚瑟·科恩伯格发现了 DNA 的生物合成机制,并因其这一贡献获得了 1959 年诺贝尔生理学或医学奖,其中包括分离和鉴定大肠杆菌 DNA 聚合酶 I。现在哺乳动物细胞中已知有 15 种 DNA 聚合酶,它们属于四个不同的家族。这些 DNA 聚合酶在许多不同的细胞过程中发挥作用,包括 DNA 复制、DNA 修复和损伤容忍。几项生化和细胞生物学研究使用基因靶向技术改变聚合酶基因的小鼠模型,进一步探讨了 DNA 聚合酶的功能。携带突变等位基因的小鼠的表型揭示了 DNA 聚合酶在胚胎发生、预防早衰和癌症抑制中的重要作用。