title: Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair.
abstract: To understand the mechanism involved in the coordination of the sequential repair reactions that lead to long-patch BER, we have investigated interactions between proteins involved in this pathway. We find that human AP endonuclease 1 (APE1) physically interacts with flap endonuclease 1 (FEN1) and with proliferating cell nuclear antigen. An oligonucleotide substrate containing a reduced abasic site, which was pre-incised with APE1, was employed to reconstitute the excision step of long-patch BER with purified human DNA polymerase beta and FEN1. We demonstrate that addition of APE1 to the excision reaction mixture slightly (1.5-2-fold) stimulates the removal of the displaced flap by FEN1. These results suggest the possibility that long-patch BER is coordinated and directed by protein-protein interactions.
authors.affiliation: MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK.
authors.forename: I I
authors.initials: II
authors.lastname: Dianova
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
authors.forename: G L
authors.initials: GL
authors.lastname: Dianov
mesh_terms: D019757:Carbon-Oxygen Lyases / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000276:immunology / Q000378:metabolism*; D045585:Flap Endonucleases; D006801:Humans; D011233:Precipitin Tests; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019951:DNA Polymerase beta; D004706:Endodeoxyribonucleases; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase