摘要
DNA polymerases (Pols) act as key players in DNA metabolism. These enzymes are the only biological macromolecules able to duplicate the genetic information stored in the DNA and are absolutely required every time this information has to be copied, as during DNA replication or during DNA repair, when lost or damaged DNA sequences have to be replaced with “original” or “correct” copies. In each DNA repair pathway one or more specific Pols are required. A feature of mammalian DNA repair pathways is their redundancy. The failure of one of these pathways can be compensated by another one. However, several DNA lesions require a specific repair pathway for error free repair. In many tumors one or more DNA repair pathways are affected, leading to error prone repair of some kind of lesions by alternatives routes, thus leading to accumulation of mutations and contributing to genomic instability, a common feature of cancer cell. In this chapter, we present the role of each Pol in genome maintenance and highlight the connections between the malfunctioning of these enzymes and cancer progress.
摘要译文
DNA聚合酶(Pols)作为DNA代谢的关键参与者。这些酶是唯一能够复制存储在DNA中的遗传信息的生物大分子,并且每次必须复制这些信息时绝对需要这些酶,如在DNA复制期间或在DNA修复期间,当丢失或损坏的DNA序列必须用“原始”或“正确”拷贝代替时。在每个DNA修复途径中,需要一个或多个特定的Pols。哺乳动物DNA修复途径的一个特征是它们的冗余。其中一条途径的失败可以由另一条路径弥补。然而,几个DNA损伤需要特定的修复途径来进行无错修复。在许多肿瘤中,一个或多个DNA修复途径受到影响,导致通过替代途径导致某些病变的错误修复,从而导致突变的积累和造成基因组不稳定性,这是癌细胞的共同特征。在这一章当中,我们介绍了每个Pol在基因组维护中的作用,并强调了这些酶失效与癌症进展之间的联系。
Emmanuele Crespan1;Alessandra Amoroso1;Giovanni Maga1. DNA Polymerases and Mutagenesis in Human Cancers. Genome Stability and Human Diseases[M].DE: Springer, 2010: 165-188