- 作者: Emmanuel A. Fausta,b, Henry Triller a
- 作者服務機構: a Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, McGill AIDS Center, b Department of Medicine, McGill University, Montreal, Canada
- 中文摘要: --
- 英文摘要: was further decreased 3-fold by HIV-1 integrase. The rateof removal of 5'-flaps by FEN-1 from post-repair HIV-1integration intermediates containing relatively long (7-nucleotide) unpaired 5'-tails and short (1-nucleotide)gaps was increased 3-fold relative to that seen with pre-repair substrates and was further stimulated 5-to 10-foldby HIV-1 integrase. Overall, post-repair structures werecleaved 18 times more effectively in the presence ofHIV-1 integrase than pre-repair structures. The site ofcleavage was 1 or 2 nucleotides 3' of the branch pointand was unaffected by HIV-1 integrase. Integrase alonehad no detectable activity in removing 5'-flaps from ei-ther pre-or post-repair substrates.Human immunodeficiency virus type 1 (HIV-1) DNA inte-gration intermediates consist of viral and host DNA seg-ments separated by a 5-nucleotide gap adjacent to a5'-AC unpaired dinucleotide. These short-flap (pre-re-pair) integration intermediates are structurally similar toDNA loci undergoing long-patch base excision repair inmammalian cells. The cellular proteins flap endonu-clease 1 (FEN-1), proliferating cell nuclear antigen, repli-cation factor C, DNA ligase I and DNA polymerase deltaare required for the repair of this type of DNA lesion. Therole of FEN-1 in the base excision repair pathway is tocleave 5'-unpaired flaps in forked structures so that DNAligase can seal the single-stranded breaks that remainfollowing gap repair. The rate of excision by FEN-1 of 5'-flaps from short- and long-flap oligonucleotide sub-strates that mimic pre- and post-repair HIV-1 integrationintermediates, respectively, and the effect of HIV-1 inte-grase on these reactions were examined in the presentstudy. Cleavage of 5'-flaps by FEN-1 in pre-repair HIV-1integration intermediates was relatively inefficient and
- 中文關鍵字: --
- 英文關鍵字: HIV-1, Integration, DNA repair, FEN-1