Three DNA Polymerases, Recruited by Different Mechanisms, Carry Out NER Repair Synthesis in Human Cells
Three DNA Polymerases, Recruited by Different Mechanisms, Carry Out NER Repair Synthesis in Human Cells
复制标题
DOI：
10.1016/j.molcel.2010.02.009
复制
发表时间：
2010-03-12
期刊：
影响因子：
16
通讯作者：
Lehmann, Alan R.
中科院分区：
文献类型：
--
作者：
Ogi, Tomoo;Limsirichaikul, Siripan;Lehmann, Alan R.
核苷酸切除修复（NER）是最通用的DNA修复系统，处理DNA中的主要紫外光产物，以及许多其他DNA加合物。NER的早期步骤已经很好理解，而修复合成和连接的后期步骤还没有。特别是，哪些聚合酶肯定参与修复合成以及它们如何被招募到受损位点尚未确定。我们报告说，在人类成纤维细胞中，大约一半的修复合成需要pol kappa和pol delta，这两种聚合酶可以在相同的修复复合物中回收。Pol κ通过泛素化的PCNA和XRCC 1被募集到修复位点，Pol δ通过经典复制因子复合物RFC 1-RFC与聚合酶辅助因子p66和未修饰的PCNA一起被募集到修复位点。剩余的修复合成依赖于聚合酶，聚合酶的募集依赖于替代的夹钳加载器CTF 18-RFC。
Nucleotide excision repair (NER) is the most versatile DNA repair system that deals with the major UV photoproducts in DNA, as well as many other DNA adducts. The early steps of NER are well understood, whereas the later steps of repair synthesis and ligation are not. In particular, which polymerases are definitely involved in repair synthesis and how they are recruited to the damaged sites has not yet been established. We report that, in human fibroblasts, approximately half of the repair synthesis requires both pol kappa and pol delta, and both polymerases can be recovered in the same repair complexes. Pol kappa is recruited to repair sites by ubiquitinated PCNA and XRCC1 and pol delta by the classical replication factor complex RFC1-RFC, together with a polymerase accessory factor, p66, and unmodified PCNA. The remaining repair synthesis is dependent on pol epsilon, recruitment of which is dependent on the alternative clamp loader CTF18-RFC.