Processing of an HIV Replication Intermediate by the Human DNA Replication Enzyme FEN1

• Published in: The Journal of biological chemistry Vol. 273; no. 44; pp. 28740 - 28745
• Main Authors: Rumbaugh, Jeffrey A., Fuentes, Gloria M., Bambara, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.10.1998; American Society for Biochemistry and Molecular Biology
• Subjects: AIDS/HIV; Base Sequence; DNA - metabolism; DNA Ligase ATP; DNA Ligases - metabolism; DNA Primers; DNA Repair; DNA, Single-Stranded - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Exodeoxyribonuclease V; Exodeoxyribonucleases - chemistry; Exodeoxyribonucleases - metabolism; Flap Endonucleases; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Protein Processing, Post-Translational; Protein Structure, Secondary; Recombinant Proteins - chemistry; Virus Replication
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.44.28740

The role of human FEN1 (flapendonuclease-1), an RTH1 (RADtwo 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 ε, 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.