van Loon Barbara, Hübscher Ulrich, Maga Giovanni
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU) , Erling Skjalgssons gt 1, N-7491 Trondheim, Norway.
Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim University Hospital , 7491 Trondheim, Norway.
Chem Res Toxicol. 2017 Nov 20;30(11):1936-1941. doi: 10.1021/acs.chemrestox.7b00152. Epub 2017 Sep 8.
In human cells, only four DNA polymerases (pols) are necessary and sufficient for the duplication of the genetic information. However, more than a dozen DNA pols are required to maintain its integrity. Such a high degree of specialization makes DNA repair pols able to cope with specific lesions or repair pathways. On the other hand, the same DNA pols can have partially overlapping roles, which could result in possible conflicts of functions, if the DNA pols are not properly regulated. DNA pol λ is a typical example of such an enzyme. It is a multifunctional enzyme, endowed with special structural and biochemical properties, which make it capable of participating in different DNA repair pathways such as base excision repair, nonhomologous end joining, and translesion synthesis. However, when mutated or deregulated, DNA pol λ can also be a source of genetic instability. Its multiple roles in DNA damage tolerance and its ability in promoting tumor progression make it also a possible target for novel anticancer approaches.
在人类细胞中，仅四种DNA聚合酶（pols）对于遗传信息的复制而言是必要且充分的。然而，维持其完整性则需要十几种DNA pols。如此高度的专业化使得DNA修复pols能够应对特定的损伤或修复途径。另一方面，相同的DNA pols可能具有部分重叠的作用，如果DNA pols未得到适当调控，这可能导致功能冲突。DNA pol λ就是这种酶的典型例子。它是一种多功能酶，具有特殊的结构和生化特性，使其能够参与不同的DNA修复途径，如碱基切除修复、非同源末端连接和跨损伤合成。然而，当发生突变或失调时，DNA pol λ也可能成为遗传不稳定的来源。它在DNA损伤耐受中的多种作用以及促进肿瘤进展的能力使其也成为新型抗癌方法的一个可能靶点。
