The wonders of flap endonucleases: structure, function, mechanism and regulation.
The wonders of flap endonucleases: structure, function, mechanism and regulation.
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DOI：
10.1007/978-94-007-4572-8_16
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Shen, Binghui
中科院分区：
文献类型：
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作者：
Finger, L David;Atack, John M;Shen, Binghui
冈崎片段的加工完成滞后链DNA合成需要几种蛋白质之间的协调。DNA聚合酶α合成的RNA引物和DNA被DNA聚合酶δ取代，产生分叉的核酸结构，称为5 ′-瓣。这些5 '-瓣被瓣核酸内切酶1（FEN）去除，瓣核酸内切酶1是一种结构特异性核酸酶，其二价金属离子依赖性磷酸二酯酶活性以精确的特异性切割5'-瓣。FEN是5'核酸酶超家族的范例，其成员使用显示共同生物化学性质和结构特征的类似核酸酶核心结构域在核酸代谢中发挥各种各样的作用。FEN结构进行详细审查，以显示如何发生DNA底物识别和FEN如何实现在一个单一的磷酸二酯裂解。一个建议的双核苷酸解配对陷阱（DoNUT）进行了讨论，关于FEN和更广泛的5'核酸酶超家族相关。同源三聚体增殖细胞核抗原蛋白（PCNA）通过在冈崎片段成熟期间促进每种蛋白质之间的传递中间体来协调DNA聚合酶、FEN和DNA连接酶的作用，以最大化通量并最小化中间体释放到更广泛的细胞环境中的后果。FEN有许多伴侣蛋白，调节和控制其在DNA复制过程中的作用，也受到几个翻译后修饰事件的控制，所有这些都在DNA复制过程中保持冈崎片段中间体的精确和适当的切割。
Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and DNA synthesised by DNA polymerase alpha are displaced by DNA polymerase delta to create bifurcated nucleic acid structures known as 5'-flaps. These 5'-flaps are removed by Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves 5'-flaps with exquisite specificity. FENs are paradigms for the 5' nuclease superfamily, whose members perform a wide variety of roles in nucleic acid metabolism using a similar nuclease core domain that displays common biochemical properties and structural features. A detailed review of FEN structure is undertaken to show how DNA substrate recognition occurs and how FEN achieves cleavage at a single phosphate diester. A proposed double nucleotide unpairing trap (DoNUT) is discussed with regards to FEN and has relevance to the wider 5' nuclease superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation to maximise through-put and minimise consequences of intermediates being released into the wider cellular environment. FEN has numerous partner proteins that modulate and control its action during DNA replication and is also controlled by several post-translational modification events, all acting in concert to maintain precise and appropriate cleavage of Okazaki fragment intermediates during DNA replication.