Rumbaugh J A, Fuentes G M, Bambara R A
Department of Biochemistry, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
J Biol Chem. 1998 Oct 30;273(44):28740-5. doi: 10.1074/jbc.273.44.28740.
The role of human FEN1 (flap endonuclease-1), an RTH1 (RAD two homolog-1) class nuclease, in the replication of human immunodeficiency virus (HIV) type 1 has been examined using model substrates. FEN1 is able to endonucleolytically cleave a primer annealed to a template, but with a 5'-unannealed tail. The HIV (+)-strand is synthesized as two discontinuous segments, with the upstream segment displacing the downstream segment to form a central (+)-strand overlap. Given a substrate with the exact HIV nucleotide sequence, FEN1 was able to remove the overlap. After extension of the upstream primer with DNA polymerase epsilon, human DNA ligase I was able to complete the continuous double strand as would occur for an integrated provirus. FEN1 may represent a target for new therapeutic interventions.
人类FEN1（瓣状核酸内切酶-1）是一种RTH1（RAD2同源物-1）类核酸酶，其在1型人类免疫缺陷病毒（HIV）复制中的作用已通过模型底物进行了研究。FEN1能够对与模板退火的引物进行内切核酸酶切割，但该引物带有5'-未退火尾巴。HIV（+）链作为两个不连续片段合成，上游片段取代下游片段形成中央（+）链重叠。对于具有确切HIV核苷酸序列的底物，FEN1能够去除重叠部分。在用DNA聚合酶ε延伸上游引物后，人类DNA连接酶I能够完成连续双链，就像整合的原病毒那样。FEN1可能是新治疗干预措施的一个靶点。
