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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

DNA double strand break repair enzymes function at multiple steps in retroviral infection

http://hdl.handle.net/10091/10784
http://hdl.handle.net/10091/10784
9185716e-02a6-4dda-a942-59214827192a
名前 / ファイル ライセンス アクション
DNA_double_strand_break.pdf DNA_double_strand_break.pdf (746.6 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2010-11-16
タイトル
タイトル DNA double strand break repair enzymes function at multiple steps in retroviral infection
言語
言語 eng
DOI
関連識別子 https://doi.org/10.1186/1742-4690-6-114
関連名称 10.1186/1742-4690-6-114
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Sakurai, Yasuteru

× Sakurai, Yasuteru

en Sakurai, Yasuteru

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Komatsu, Kenshi

× Komatsu, Kenshi

en Komatsu, Kenshi

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Agematsu, Kazunaga

× Agematsu, Kazunaga

en Agematsu, Kazunaga

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Matsuoka, Masao

× Matsuoka, Masao

en Matsuoka, Masao

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出版者
出版者 BIOMED CENTRAL LTD
引用
内容記述 Retrovirology. 6:114 (2009)
書誌情報 Retrovirology

巻 6, 発行日 2009-12-15
内容記述
内容記述タイプ Other
内容記述 (c) 2009 Sakurai et al; licensee BioMed Central Ltd. / This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
抄録
内容記述 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.
資源タイプ(コンテンツの種類)
ISSN
収録物識別子タイプ PISSN
収録物識別子 1742-4690
書誌レコードID
収録物識別子タイプ NCID
収録物識別子 AA12051445
PubMed
識別子タイプ PMID
関連識別子 https://pubmed.ncbi.nlm.nih.gov/20003485
関連名称 20003485
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
WoS
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000273059000001
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