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Phosphorylation affects the biological activity of the integrase of the P2-likephage ΦD145
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. (Genetics,Microbiology and Toxicology)
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
(English)Manuscript (preprint) (Other academic)
Keyword [en]
Integrase, Phage ΦD145; Protein phosphorylation; Wzc
Identifiers
URN: urn:nbn:se:su:diva-45939OAI: oai:DiVA.org:su-45939DiVA: diva2:370485
Available from: 2010-11-16 Created: 2010-11-16 Last updated: 2010-11-17Bibliographically approved
In thesis
1. Site-specific recombination of P2-like phages; possible tools for safe gene therapy: A focus on phage ΦD145
Open this publication in new window or tab >>Site-specific recombination of P2-like phages; possible tools for safe gene therapy: A focus on phage ΦD145
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

P2-like bacteriophages integrate their genome into the E. coli host cell by a site-specific recombination event upon lysogenization. The integrative recombination occurs between a specific sequence in the phage genome, attP, and a specific sequence in the host genome, attB, generating the host-phage junctions attL and attR. The integration is mediated by the phage enzyme integrase (Int) and the host factor IHF. The excisive recombination takes place between attL and attR, and is mediated by Int, IHF and phage encoded protein Cox. For safe integration of foreign genes into eukaryotic chromosome a recombinases is necessary which can perform the integration site-specifically. P2-like phage integrases have the potential to become tools for safe gene therapy. Their target is simple but specific, and once integration has occurred it is very stable in the absence of the Cox protein. The site-specific recombination mechanism has to be understood at the molecular level. Therefore, I have initiated the characterization of the site-specific recombination system of the P2-like phage ΦD145. In this work, Int and IHF are shown to bind to the different attachment sites cooperatively. One of two possible inverted repeats in attP is shown to be the Int core recognition site. The attP core of this phage has high identity with a site on human chromosome, denoted as ΨattB. In this study we have shown that in in vivo recombination ΦD145 Int can accept ΨattB in both bacteria and in eukaryotic cells. Also shown that Int consists of an intrinsic nuclear localization signal. A study also reveled that ΦD145 Int activity was affected by the Tyr-phosphorylation. Attempts have been made to change the specificity of the other P2-like phage P2 and WΦ integrases and also structural and functional analysis was done. A study on comparative analysis of Cox proteins and Cox binding sites gave us the basic information about the recombination mechanism.

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University, 2010. 50 p.
Keyword
bacteriophage, integrase, site-specific recombination
National Category
Natural Sciences
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-45940 (URN)978-91-7447-174-8 (ISBN)
Public defence
2010-12-17, sal E306, Arrheniuslaboratorierna, Svante Arrhenius väg 20 C, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.Available from: 2010-11-25 Created: 2010-11-16 Last updated: 2010-11-17Bibliographically approved

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