Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford OX1 3RE, UK.
Biochem Soc Trans. 2011 Jan;39(1):70-6. doi: 10.1042/BST0390070.
Efficient processing of Okazaki fragments generated during discontinuous lagging-strand DNA replication is critical for the maintenance of genome integrity. In eukaryotes, a number of enzymes co-ordinate to ensure the removal of initiating primers from the 5'-end of each fragment and the generation of a covalently linked daughter strand. Studies in eukaryotic systems have revealed that the co-ordination of DNA polymerase δ and FEN-1 (Flap Endonuclease 1) is sufficient to remove the majority of primers. Other pathways such as that involving Dna2 also operate under certain conditions, although, notably, Dna2 is not universally conserved between eukaryotes and archaea, unlike the other core factors. In addition to the catalytic components, the DNA sliding clamp, PCNA (proliferating-cell nuclear antigen), plays a pivotal role in binding and co-ordinating these enzymes at sites of lagging-strand replication. Structural studies in eukaryotic and archaeal systems have revealed that PCNA-binding proteins can adopt different conformations when binding PCNA. This conformational malleability may be key to the co-ordination of these enzymes' activities.
有效处理不连续滞后链 DNA 复制过程中产生的冈崎片段对于维持基因组完整性至关重要。在真核生物中，许多酶协同作用以确保从每个片段的 5' 端去除起始引物，并生成共价连接的子链。真核生物系统的研究表明，DNA 聚合酶 δ 和 FEN-1（Flap Endonuclease 1）的协调足以去除大多数引物。其他途径，如涉及 Dna2 的途径，在某些条件下也起作用，尽管值得注意的是，与其他核心因子不同，Dna2在真核生物和古菌之间并非普遍保守。除了催化成分外，DNA 滑动夹 PCNA（增殖细胞核抗原）在滞后链复制位点结合和协调这些酶方面发挥着关键作用。真核生物和古菌系统的结构研究表明，PCNA 结合蛋白在结合 PCNA 时可以采用不同的构象。这种构象的可塑性可能是协调这些酶活性的关键。
