Goodman Myron F
Department of Biological Sciences and Chemistry, Hedco Molecular Biology Laboratory, University of Southern California, Los Angeles, California 90089-1340, USA.
Annu Rev Biochem. 2002;71:17-50. doi: 10.1146/annurev.biochem.71.083101.124707. Epub 2001 Nov 9.
DNA repair is crucial to the well-being of all organisms from unicellular life forms to humans. A rich tapestry of mechanistic studies on DNA repair has emerged thanks to the recent discovery of Y-family DNA polymerases. Many Y-family members carry out aberrant DNA synthesis-poor replication accuracy, the favored formation of non-Watson-Crick base pairs, efficient mismatch extension, and most importantly, an ability to replicate through DNA damage. This review is devoted primarily to a discussion of Y-family polymerase members that exhibit error-prone behavior. Roles for these remarkable enzymes occur in widely disparate DNA repair pathways, such as UV-induced mutagenesis, adaptive mutation, avoidance of skin cancer, and induction of somatic cell hypermutation of immunoglobulin genes. Individual polymerases engaged in multiple repair pathways pose challenging questions about their roles in targeting and trafficking. Macromolecular assemblies of replication-repair "factories" could enable a cell to handle the complex logistics governing the rapid migration and exchange of polymerases.
DNA修复对于从单细胞生命形式到人类的所有生物体的健康都至关重要。由于最近发现了Y家族DNA聚合酶,关于DNA修复的大量机制研究应运而生。许多Y家族成员进行异常的DNA合成——复制准确性差、倾向于形成非沃森-克里克碱基对、高效错配延伸,最重要的是,具有通过DNA损伤进行复制的能力。本综述主要致力于讨论表现出易错行为的Y家族聚合酶成员。这些非凡酶的作用出现在广泛不同的DNA修复途径中,如紫外线诱导的诱变、适应性突变、避免皮肤癌以及诱导免疫球蛋白基因的体细胞超突变。参与多种修复途径的单个聚合酶对其在靶向和运输中的作用提出了具有挑战性的问题。复制-修复“工厂”的大分子组装可能使细胞能够处理控制聚合酶快速迁移和交换的复杂物流。