Nazarkina Zh K, Lavrik O I, Khodyreva S N
Mol Biol (Mosk). 2008 May-Jun;42(3):405-21.
Flap endonuclease-1 (FEN1) is a structure specific endonuclease. The natural substrates of FEN1 are 5'-flap structures formed by three DNA chains one of them has unannealed flapped 5'-end (flap). Flap structures are the intermediates of different processes of DNA metabolism, such as DNA recombination, Okazaki fragment maturation during replication of lagging strand, as well as strand displacement DNA synthesis in base excision repair. FEN1 also possesses 5'-exonuclease activity and newly discovered gap endonuclease activity. FEN1 is known to interact physically and functionally with a number of DNA replication and repair proteins such as the proliferating cell nuclear antigen, helicase/nuclease Dna2, WRN and BLM proteins, replication protein A, apurinic/apyrimidinic endonuclease 1, DNA polymerase beta, poly(ADP-riboso) polymerase 1, high mobility group protein 1, integrase of human immunodeficiency virus, transcription coactivator p300, chromatin proteins, cyclin-dependent kinases (Cdk1, Cdk2, Cyclin A). FEN1 activity is significant for maintaining the integrity of repeat sequences in genome. Recent data suppose the correlation between the abnormality of hFEN1 activity and arising/progression of neurodegenerative and cancer diseases. FEN1 has the dramatic effect on cell growth and development thereby attracting the interest to this enzyme.
翼端核酸内切酶1(FEN1)是一种结构特异性核酸内切酶。FEN1的天然底物是由三条DNA链形成的5' - 翼结构,其中一条链具有未退火的带翼5'末端(翼)。翼结构是DNA代谢不同过程的中间体,如DNA重组、滞后链复制过程中的冈崎片段成熟,以及碱基切除修复中的链置换DNA合成。FEN1还具有5' - 核酸外切酶活性和新发现的缺口核酸内切酶活性。已知FEN1在物理和功能上与许多DNA复制和修复蛋白相互作用,如增殖细胞核抗原、解旋酶/核酸酶Dna2、WRN和BLM蛋白、复制蛋白A、脱嘌呤/脱嘧啶内切酶1、DNA聚合酶β、聚(ADP - 核糖)聚合酶1、高迁移率族蛋白1、人类免疫缺陷病毒整合酶、转录共激活因子p300、染色质蛋白、细胞周期蛋白依赖性激酶(Cdk1、Cdk2、细胞周期蛋白A)。FEN1活性对于维持基因组中重复序列的完整性很重要。最近的数据表明hFEN1活性异常与神经退行性疾病和癌症疾病的发生/进展之间存在相关性。FEN1对细胞生长和发育具有显著影响,因此引起了人们对这种酶的兴趣。