AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination
| Autor: | Mikiyo Nakata, Kazuo Kinoshita, Hitoshi Nagaoka, Reiko Shinkura, Maki Kobayashi, Andre Stanlie, Yoko Kitawaki, Nasim A. Begum, Masamichi Muramatsu, Tomomitsu Doi, Tasuku Honjo, Lucia Kato, Il-mi Okazaki, Masatoshi Aida |
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| Rok vydání: | 2009 |
| Předmět: |
Cleavage factor
Cleavage and polyadenylation specificity factor In Vitro Techniques Topoisomerase-I Inhibitor Cleavage (embryo) Cell Line Mice chemistry.chemical_compound Cytidine Deaminase Animals RNA Messenger RNA Small Interfering Mice Knockout B-Lymphocytes Multidisciplinary biology Topoisomerase DNA Cytidine deaminase Biological Sciences Immunoglobulin Class Switching Molecular biology Mice Inbred C57BL DNA Topoisomerases Type I chemistry Protein Biosynthesis biology.protein Nucleic Acid Conformation DNA supercoil Camptothecin Topoisomerase I Inhibitors |
| Zdroj: | Proceedings of the National Academy of Sciences. 106:22375-22380 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0911879106 |
| Popis: | To initiate class switch recombination (CSR) activation-induced cytidine deaminase (AID) induces staggered nick cleavage in the S region, which lies 5 to each Ig constant region gene and is rich in palindromic sequences. Topoisomerase 1 (Top1) controls the supercoiling of DNA by nicking, rotating, and religating one strand of DNA. Curiously, Top1 reduction or AID overexpression causes the genomic instability. Here, we report that the inactivation of Top1 by its specific inhibitor camptothecin drastically blocked both the S region cleavage and CSR, indicating that Top1 is responsible for the S region cleavage in CSR. Surprisingly, AID expression suppressed Top1 mRNA translation and reduced its protein level. In addition, the decrease in the Top1 protein by RNA-mediated knockdown augmented the AID-dependent S region cleavage, as well as CSR. Furthermore, Top1 reduction altered DNA structure of the S region. Taken together, AID-induced Top1 reduction alters S region DNA structure probably to non-B form, on which Top1 can introduce nicks but cannot religate, resulting in S region cleavage. AIDによるクラススイッチの際DNA切断を起こすのはトポイソメラーゼ1であることを発見. 京都大学プレスリリース. 2009-12-08. |
| Databáze: | OpenAIRE |
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