Shcherbakova Polina V, Bebenek Katarzyna, Kunkel Thomas A
Laboratory of Molecular Genetics at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Sci Aging Knowledge Environ. 2003 Feb 26;2003(8):RE3. doi: 10.1126/sageke.2003.8.re3.
A major function of DNA polymerases is to accurately replicate the six billion nucleotides that constitute the human genome. This task is complicated by the fact that the genome is constantly challenged by a variety of endogenous and exogenous DNA-damaging agents. DNA damage can block DNA replication or alter base coding potential, resulting in mutations. In addition, the accumulation of damage in nonreplicating DNA can affect gene expression, which leads to the malfunction of many cellular processes. A number of DNA repair systems operate in cells to remove DNA lesions, and several DNA polymerases are known to be the key components of these repair systems. In the past few years, a number of novel DNA polymerases have been discovered that likely function in replicative bypass of DNA damage missed by DNA repair enzymes or in specialized forms of repair. Furthermore, DNA polymerases can act as sensors in cell cycle checkpoint pathways that prevent entry into mitosis until damaged DNA is repaired and replication is completed. The list of DNA template-dependent eukaryotic DNA polymerases now consists of 14 enzymes with amazingly different properties. In this review, we discuss the possible functions of these polymerases in DNA damage repair, the replication of intact and damaged chromosomes, and cell cycle checkpoints.
DNA聚合酶的一个主要功能是精确复制构成人类基因组的60亿个核苷酸。这项任务因基因组不断受到各种内源性和外源性DNA损伤剂的挑战而变得复杂。DNA损伤会阻碍DNA复制或改变碱基编码潜能，从而导致突变。此外，非复制性DNA中损伤的积累会影响基因表达，进而导致许多细胞过程功能失调。细胞中有多种DNA修复系统发挥作用以去除DNA损伤，并且已知几种DNA聚合酶是这些修复系统的关键组成部分。在过去几年中，已经发现了一些新型DNA聚合酶，它们可能在DNA修复酶遗漏的DNA损伤的复制性跨越或特殊形式的修复中发挥作用。此外，DNA聚合酶可在细胞周期检查点途径中充当传感器，防止进入有丝分裂，直到受损DNA修复且复制完成。目前，依赖DNA模板的真核生物DNA聚合酶列表包含14种酶，它们具有惊人的不同特性。在本综述中，我们讨论了这些聚合酶在DNA损伤修复、完整和受损染色体复制以及细胞周期检查点中的可能功能。
