DNA double strand break repair enzymes function at multiple steps in retroviral infection.
スポンサーリンク
概要
- 論文の詳細を見る
BACKGROUND: DNA double strand break (DSB) repair enzymes are thought to be necessary for retroviral infection, especially for the post-integration repair and circularization of viral cDNA. However, the detailed roles of DSB repair enzymes in retroviral infection remain to be elucidated. RESULTS: A GFP reporter assay showed that the infectivity of an HIV-based vector decreased in ATM- and DNA-PKcs-deficient cells when compared with their complemented cells, while that of an MLV-based vector was diminished in Mre11- and DNA-PKcs-deficient cells. By using a method based on inverse- and Alu-PCR, we analyzed sequences around 3' HIV-1 integration sites in ATM-, Mre11- and NBS1- deficient cells. Increased abnormal junctions between the HIV-1 provirus and the host DNA were found in these mutant cell lines compared to the complemented cell lines and control MRC5SV cells. The abnormal junctions contained two types of insertions: 1) GT dinucleotides, which are normally removed by integrase during integration, and 2) inserted nucleotides of unknown origin. Artemis-deficient cells also showed such abnormalities. In Mre11-deficient cells, part of a primer binding site sequence was also detected. The 5' host-virus junctions in the mutant cells also contained these types of abnormal nucleotides. Moreover, the host-virus junctions of the MLV provirus showed similar abnormalities. These findings suggest that DSB repair enzymes play roles in the 3'-processing reaction and protection of the ends of viral DNA after reverse transcription. We also identified both 5' and 3' junctional sequences of the same provirus by inverse PCR and found that only the 3' junctions were abnormal with aberrant short repeats, indicating that the integration step was partially impaired in these cells. Furthermore, the conserved base preferences around HIV-1 integration sites were partially altered in ATM-deficient cells. CONCLUSIONS: These results suggest that DSB repair enzymes are involved in multiple steps including integration and pre-integration steps during retroviral replication.
論文 | ランダム
- 岐阜県初の高齢者向け優良賃貸住宅「リコシエ村」 (特集 平成17年度高齢者住宅担当者研修会)
- 高齢者等支援施設を併設した高齢者向け優良賃貸住宅について (特集 平成17年度高齢者住宅担当者研修会)
- 高齢者専用賃貸住宅の登録制度について (特集 福祉政策と住宅政策との連携)
- 経営は山あり谷あり 失敗を活かす!(5)主婦から転身、奈良県トップの賃貸住宅仲介企業の社長に 山晃住宅社長 前田祥子
- 編集部レポート 様変わりした!! 学生賃貸住宅ニーズ最新事情